Showing papers in "Diabetic Medicine in 2008"

Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta‐analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion

Abstract: Aims Continuous subcutaneous insulin infusion (CSII) is a recommended treatment for reducing severe hypoglycaemia in Type 1 diabetes, but the change in hypoglycaemia compared with multiple daily insulin injections (MDI) is unclear. We therefore conducted a meta-analysis comparing severe hypoglycaemia and glycaemic control during CSII and MDI. Methods Databases and literature (1996–2006) were searched for randomized controlled trials (RCTs) and before/after studies of ≥ 6 months’ duration CSII and with severe hypoglycaemia frequency > 10 episodes/100 patient years on MDI. Results In 22 studies (21 reports), severe hypoglycaemia during MDI was related to diabetes duration (P = 0.038) and was greater in adults than children (100 vs. 36 events/100 patient years, P = 0.036). Severe hypoglycaemia was reduced during CSII compared with MDI, with a rate ratio of 2.89 (95% CI 1.45 to 5.76) for RCTs and 4.34 (2.87 to 6.56) for before/after studies [rate ratio 4.19 (2.86 to 6.13) for all studies]. The reduction was greatest in those with the highest initial severe hypoglycaemia rates on MDI (P < 0.001). The mean difference in glycated haemoglobin (HbA1c) between treatments was less for RCTs [0.21% (0.13–0.30%)] than in before/after studies [0.72% (0.55–0.90%)] but strongly related to the initial HbA1c on MDI (P < 0.001). Conclusions The severe hypoglycaemia rate in Type 1 diabetes was markedly less during CSII than MDI, with the greatest reduction in those with most severe hypoglycaemia on MDI and those with the longest duration of diabetes. The biggest improvement in HbA1c was in those with the highest HbA1c on MDI.

Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels.

Abstract: Aims To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels. Methods Double-blind, parallel group, placebo-controlled randomized trial. A single dose of 100 000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter, when levels of circulating 25-hydroxyvitamin D were likely to be lowest. Patients were enrolled if their baseline 25-hydroxyvitamin D level was < 50 nmol/l. Endothelial function and blood pressure were measured and fasting blood samples were taken at baseline and 8 weeks after administration of vitamin D. Results Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels < 50 nmol/l. Thirty-four subjects completed the study, with a mean age of 64 years and a baseline 25-hydroxyvitamin D level of 38.3 nmol/l. Vitamin D supplementation increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation (FMD) of the brachial artery by 2.3%. The improvement in FMD remained significant after adjusting for changes in blood pressure. Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo; this did not correlate with change in FMD. Conclusions Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotland. A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency.

Hypoglycaemia in Type 2 diabetes

Abstract: The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication—in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self-reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes—both direct hospital costs and indirect costs—are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications. Diabet. Med. 25, 245–254 (2008)

A longitudinal study of affective and anxiety disorders, depressive affect and diabetes distress in adults with Type 2 diabetes

Abstract: Aims To report the prevalence and correlates of affective and anxiety disorders, depressive affect and diabetes distress over time.

Prevalence of impaired awareness of hypoglycaemia in adults with Type 1 diabetes.

Abstract: Aims Impaired awareness of hypoglycaemia (IAH) is thought to affect approximately 25% of people with Type 1 diabetes. While this estimate was based on retrospective information from patients in several small studies performed several years ago, validated methods of assessment have not been used in a large hospital clinic-based population to ascertain the prevalence in the present era. Methods Five hundred and eighteen people with Type 1 diabetes were recruited by random selection over a 2-year period. Participants completed a questionnaire documenting baseline characteristics and assessment of their awareness status using the method described by Gold et al. The number of episodes of severe hypoglycaemia they had experienced in the preceding year was recorded retrospectively. Results IAH was present in 19.5% of the cohort. Compared to those with normal awareness of hypoglycaemia, those with IAH were significantly older [mean ± standard deviation (sd); 39.3 ± 12.9 vs. 45.9 ± 13.5 years, P < 0.001], had a longer duration of diabetes [median (interquartile range) 14 (8–22) vs. 23 (14–32) years, P < 0.001], and had a six-fold higher frequency of severe hypoglycaemia in the previous year [0.38 ± 1.04 (25th–75th centile 0–0) vs. 2.36 ± 4.81 (25th–75th centile 0–2) episodes per person, P < 0.001]. Conclusions The present survey of a large hospital-based clinic population has confirmed that a significant proportion of people with Type 1 diabetes (19.5%) continue to have IAH. Despite improvements in insulin therapies, intensification of insulin regimens and innovative patient education, the prevalence of IAH remains high in Type 1 diabetes.

Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing.

Abstract: Aims Matrix metalloproteinases (MMPs) play a major role in wound healing: they can degrade all components of the extracellular matrix. In diabetic foot ulcers there is an excess of MMPs and a decrease of the tissue inhibitors of MMPs (TIMPs). This imbalance is probably one cause of impaired healing. However, little is known about changes in MMPs during wound healing.

Prevalence and projections of diabetes and pre-diabetes in adults in Sri Lanka--Sri Lanka Diabetes, Cardiovascular Study (SLDCS).

Abstract: Aims To determine the prevalence of diabetes mellitus and pre-diabetes (impaired fasting glucose and impaired glucose tolerance) in adults in Sri Lanka. Projections for the year 2030 and factors associated with diabetes and pre-diabetes are also presented. Methods This cross-sectional study was conducted between 2005 and 2006. A nationally representative sample of 5000 adults aged ≥ 18 years was selected by a multi-stage random cluster sampling technique. Fasting plasma glucose was tested in all participants and a 75-g oral glucose tolerance test was performed in non-diabetic subjects. Prevalence was estimated for those > 20 years of age. Results Response rate was 91% (n = 4532), males 40%, age 46.1 ± 15.1 years (mean ± standard deviation). The age–sex standardized prevalence (95% confidence interval) of diabetes for Sri Lankans aged ≥ 20 years was 10.3% (9.4–11.2%) [males 9.8% (8.4–11.2%), females 10.9% (9.7–12.1%), P = 0.129). Thirty-six per cent (31.9–40.1%) of all diabetic subjects were previously undiagnosed. Diabetes prevalence was higher in the urban population compared with rural [16.4% (13.8–19.0%) vs. 8.7% (7.8–9.6%); P < 0.001]. The prevalence of overall, urban and rural pre-diabetes was 11.5% (10.5–12.5%), 13.6% (11.2–16.0%) and 11.0% (10.0–12.0%), respectively. Overall, 21.8% (20.5–23.1%) had some form of dysglycaemia. The projected diabetes prevalence for the year 2030 is 13.9%. Those with diabetes and pre-diabetes compared with normal glucose tolerance were older, physically inactive, frequently lived in urban areas and had a family history of diabetes. They had higher body mass index, waist circumference, waist–hip ratio, systolic/diastolic blood pressure, low-density lipoprotein cholesterol and triglycerides. Insulin was prescribed to 4.4% (2.7–6.1%) of all diabetic subjects. Conclusions One in five adults in Sri Lanka has either diabetes or pre-diabetes and one-third of those with diabetes are undiagnosed.

International Diabetes Federation guideline for management of postmeal glucose: a review of recommendations.

Abstract: Diabetes is a significant and growing concern, with over 246 million people around the world living with the disease and another 308 million with impaired glucose tolerance. Depending on the resources of different nations, intervention has generally focused on optimizing overall glycaemic control as assessed by glycated haemoglobin (HbA(1c)) and fasting plasma glucose (FPG) values. Nevertheless, increasing evidence supports the importance of controlling all three members of the glucose triad, namely HbA(1c), FPG and postmeal glucose (PMG) in order to improve outcome in diabetes. As part of its global mission to promote diabetes care and prevention and to find a cure, the International Diabetes Federation (IDF) recently developed a guideline that reviews evidence to date on PMG and the development of diabetic complications. Based on an extensive database search of the literature, and guided by a Steering and Development Committee including experts from around the world, the IDF Guideline for Management of Postmeal Glucose offers recommendations for appropriate clinical management of PMG. These recommendations are intended to help clinicians and organizations in developing strategies for effective management of PMG in individuals with Type 1 and Type 2 diabetes. The following review highlights the recommendations of the guideline, the supporting evidence provided and the major conclusions drawn. The full guideline is available for download at http://www.idf.org.

Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation.

Abstract: Maternally inherited diabetes and deafness (MIDD) affects up to 1% of patients with diabetes but is often unrecognized by physicians. It is important to make an accurate genetic diagnosis, as there are implications for clinical investigation, diagnosis, management and genetic counselling. This review summarizes the range of clinical phenotypes associated with MIDD; outlines the advances in genetic diagnosis and pathogenesis of MIDD; summarizes the published prevalence data and provides guidance on the clinical management of these patients and their families.

Psychological distress and risk of pre-diabetes and Type 2 diabetes in a prospective study of Swedish middle-aged men and women.

Abstract: Aims To determine the role of psychological distress as a predictor of pre-diabetes and Type 2 diabetes. Methods This cohort study comprised 2127 Swedish middle-aged men and 3100 women with baseline normal glucose tolerance measured by oral glucose tolerance test. At follow-up 8–10 years later, 245 men and 177 women had pre-diabetes [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and IFG + IGT] and Type 2 diabetes was detected in 103 men and 57 women. Baseline psychological distress was measured by an index of five questions concerning anxiety, apathy, depression, fatigue and insomnia. Odds ratios (ORs) were estimated for pre-diabetes and Type 2 diabetes in association with total psychological distress. In addition, ORs of the single-item questions were calculated. Results In men, adjusted ORs (95% confidence interval) in the highest index group of psychological distress compared with the lowest group were 1.9 (1.2–2.8) and 2.2 (1.2–4.1) for pre-diabetes and Type 2 diabetes, respectively. Corresponding estimates in women were 1.2 (0.7–2.1) and 0.5 (0.2–1.2). In the middle symptoms groups, adjusted ORs in men were 1.1 (0.8–1.4) for pre-diabetes and 1.2 (0.7–2.0) for Type 2 diabetes and in women 1.8 (1.1–3.0) and 0.7 (0.3–1.4). When analysed separately, the associations with each of the five single factors were similar. Conclusions The results indicate that psychological distress, including symptoms of anxiety, apathy, depression, fatigue and insomnia, increases the risk of pre-diabetes and Type 2 diabetes in Swedish middle-aged men. Increased risks were not present in women, except for pre-diabetes in the middle index group.

NICE guidance on diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. NICE clinical guideline 63. London, March 2008.

Abstract: The care of pregnant women with disorders of glucose metabolism is a satisfying part of diabetes care but outcomes remain less than ideal. The evidence base to improve care has grown over subsequent decades and clinicians will welcome up-to-date NICE guidance on this topic. This review looks at the guidance from the perspective of a secondary care diabetes team.

Liraglutide, a once‐daily human GLP‐1 analogue, improves pancreatic B‐cell function and arginine‐stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus

Abstract: Aims To assess the effect of liraglutide, a once-daily human glucagon-like peptide-1 analogue on pancreatic B-cell function. Methods Patients with Type 2 diabetes (n = 39) were randomized to treatment with 0.65, 1.25 or 1.9 mg/day liraglutide or placebo for 14 weeks. First- and second-phase insulin release were measured by means of the insulin-modified frequently sampled intravenous glucose tolerance test. Arginine-stimulated insulin secretion was measured during a hyperglycaemic clamp (20 mmol/l). Glucose effectiveness and insulin sensitivity were estimated by means of the insulin-modified frequently sampled intravenous glucose tolerance test. Results The two highest doses of liraglutide (1.25 and 1.9 mg/day) significantly increased first-phase insulin secretion by 118 and 103%, respectively (P < 0.05). Second-phase insulin secretion was significantly increased only in the 1.25 mg/day group vs. placebo. Arginine-stimulated insulin secretion increased significantly at the two highest dose levels vs. placebo by 114 and 94%, respectively (P < 0.05). There was no significant treatment effect on glucose effectiveness or insulin sensitivity. Conclusions Fourteen weeks of treatment with liraglutide showed improvements in first- and second-phase insulin secretion, together with improvements in arginine-stimulated insulin secretion during hyperglycaemia.

Symptoms of depression prospectively predict poorer self-care in patients with Type 2 diabetes

Abstract: AIMS To prospectively examine the association of depression symptoms with subsequent self-care and medication adherence in patients with type 2 diabetes mellitus.

Maternal vitamin D deficiency, ethnicity and gestational diabetes

Abstract: Aims Vitamin D deficiency has been linked to impaired glucose metabolism. We determined whether serum 25-hydroxyvitamin D (25OHD) is associated with glucose metabolism in pregnant women and the effect of ethnicity on this relationship. Methods We analysed serum 25OHD concentrations in 307 pregnant women attending a metropolitan obstetric clinic between October 2003 and May 2005. Measurements from 264 of the women were taken at the time of glucose tolerance testing at mid-gestation, a population therefore at increased risk for gestational diabetes. Pearson correlation analysis was used to test for univariate linear relationships between the natural log of serum 25OHD (ln-25OHD) and other variables. Multiple regression analysis was used to adjust for confounding factors. Results Mean serum 25OHD concentration was 53.8 ± 23.9 nmol/l (sd). Ln-25OHD was negatively correlated with serum parathyroid hormone as expected (r −0.24, confidence intervals −0.35 to −0.12). Ln-25OHD was also negatively correlated with fasting plasma glucose (r−0.20, −0.31 to −0.08), fasting insulin (r −0.20, −0.31 to −0.08) and insulin resistance as calculated by homeostatis model assessment (r −0.21, −0.32 to −0.09). The association between fasting glucose and log-transformed 25OHD concentration was of borderline significance after accounting for ethnicity, age and body mass index in multivariate analyses (−0.13, −0.26 to 0.01). The odds ratio of gestational diabetes in women with 25OHD < 50 nmol/l did not reach statistical significance (1.92, 95% confidence interval 0.89–4.17). Conclusions Maternal 25OHD concentrations are inversely related to fasting glucose, although further studies are required to establish whether this is independent of the effects of ethnic background.

Beneficial effects of once-daily liraglutide, a human glucagon-like peptide-1 analogue, on cardiovascular risk biomarkers in patients with Type 2 diabetes

Abstract: Liraglutide is a once-daily, human glucagon-like peptide-1 (GLP-1) analogue. Clinical studies have demonstrated blood glucose and weight-reducing effects, improvements in pancreatic B-cell function and a low risk of hypoglycaemic events with liraglutide [1,2]. Type 2 diabetes is associated with an increased risk of cardiovascular events. Recently, studies in patients with Type 2 diabetes have shown that native GLP-1 may also have beneficial effects on the myocardium [3] and on endothelial function [4]. We present here the effect of liraglutide on biomarkers for cardiovascular risk in patients with Type 2 diabetes, as an exploratory endpoint from a broader clinical study. The design and non-cardiovascular biomarker results of this study have been described previously [1]. The trial was carried out in accordance with good clinical practice. Briefly, 165 patients with Type 2 diabetes were randomized to either placebo or 0.65 mg, 1.25 mg or 1.9 mg liraglutide for 14 weeks. Across the four treatment arms, 17–23% of the subjects were previously treated with diet and exercise and the remaining subjects with oral glucose-lowering agents. Subjects had a mean body mass index (BMI) of 28.9–31.2 kg/m2 and mean glycated haemoglobin (HbA1c) at randomization of 8.1–8.5%. The study was powered against the primary endpoint HbA1c, but was not powered at an 80% level for a difference of 20% for the cardiovascular biomarkers discussed here. At randomization and end of study, the following additional parameters were assessed: adiponectin, leptin, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), plasminogen activator inhibitor 1 (PAI-1) and B-type natriuretic peptide (BNP). The data are presented in Table 1. A significant decrease in PAI-1 and BNP levels were observed following treatment with liraglutide. There was a non-significant, but dose-dependent, reduction in hs-CRP levels. There were no treatment effects on levels of adiponectin, leptin, IL-6 and TNF-α with liraglutide. Table 1 Baseline levels and change from baseline level of cardiovascular risk markers after 14 weeks of treatment This study was part of a larger clinical trial, which showed significantly improved glycaemic control and a reduction in body weight in subjects treated with liraglutide [1]. In addition, systolic blood pressure (reduction of 8 mmHg at 1.90 mg/day vs. placebo) and plasma triglycerides (reduction of 22% at 1.90 mg/day vs. placebo) were significantly reduced [1]. PAI-1 and hs-CRP are inflammatory biomarkers that are associated with an increased risk of cardiovascular disease [5]. Elevated PAI-1 levels may suppress the fibrinolytic process and thereby be associated with the development of atherosclerosis. BNP is a marker of left ventricular dysfunction and elevated levels are risk markers for cardiovascular diseases, in particular for heart failure [6]. The findings suggest that liraglutide, when used to regulate blood glucose levels in patients with Type 2 diabetes, improves certain biomarkers associated with increased cardiovascular risk. Large prospective trials are needed to confirm these results and to assess whether these effects translate into improvements in cardiovascular risk in patients with Type 2 diabetes.

Delivery of care to diabetic patients with foot ulcers in daily practice: results of the Eurodiale Study, a prospective cohort study

Abstract: Aims To determine current management and to identify patient-related factors and barriers that influence management strategies in diabetic foot disease. Methods The Eurodiale Study is a prospective cohort study of 1232 consecutive individuals presenting with a new diabetic foot ulcer in 14 centres across Europe. We determined the use of management strategies: referral, use of offloading, vascular imaging and revascularization. Results Twenty-seven percent of the patients had been treated for > 3 months before referral to a foot clinic. This varied considerably between countries (6-55%). At study entry, 77% of the patients had no or inadequate offloading. During follow-up, casting was used in 35% (0-68%) of the plantar fore- or midfoot ulcers. Predictors of use of casting were male gender, large ulcer size and being employed. Vascular imaging was performed in 56% (14-86%) of patients with severe limb ischaemia; revascularization was performed in 43%. Predictors of use of vascular imaging were the presence of infection and ischaemic rest pain. Conclusion Treatment of many patients is not in line with current guidelines and there are large differences between countries and centres. Our data suggest that current guidelines are too general and that healthcare organizational barriers and personal beliefs result in underuse of recommended therapies. Action should be undertaken to overcome these barriers and to guarantee the delivery of optimal care for the many individuals with diabetic foot disease.

Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes

Abstract: AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood. RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres

Comparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes: a 24-week, double-blind, randomized trial.

Abstract: Aims To compare the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor, vildagliptin, with the alpha glucosidase inhibitor, acarbose, in drug-naive patients with Type 2 diabetes. Methods This multi-centre, randomized, double-blind, parallel-arm study compared the efficacy and tolerability of vildagliptin (100 mg daily, given as 50 mg twice daily, n = 441) and acarbose (up to 300 mg daily, given as three equally divided doses, n = 220) during 24-week treatment in drug-naive patients with Type 2 diabetes. Results Monotherapy with vildagliptin or acarbose decreased glycated haemoglobin (HbA1c) (baseline ≈ 8.6%) to a similar extent during 24-week treatment. The adjusted mean change from baseline to end-point (AMΔ) in HbA1c was −1.4 ± 0.1% and −1.3 ± 0.1% in patients receiving vildagliptin and acarbose, respectively, meeting the statistical criterion for non-inferiority (upper limit of 95% confidence interval for between-treatment difference ≤ 0.4%). The decrease in fasting plasma glucose was similar with acarbose (−1.5 ± 0.2 mmol/l) and vildagliptin (−1.2 ± 0.1 mmol/l). Body weight did not change in vildagliptin-treated patients (−0.4 ± 0.1 kg) but decreased in acarbose-treated patients (−1.7 ± 0.2 kg, P < 0.001 vs. vildagliptin). The proportion of patients experiencing any adverse event (AE) was 35% vs. 51% in patients receiving vildagliptin or acarbose, respectively; gastrointestinal AEs were significantly more frequent with acarbose (25.5%) than vildagliptin (12.3%, P < 0.001). No hypoglycaemia was reported for either group. Conclusions Vildagliptin is effective and well tolerated in patients with Type 2 diabetes, demonstrating similar glycaemic reductions to acarbose, but with better tolerability.

Microvascular disease: what does the UKPDS tell us about diabetic nephropathy?

Abstract: The UK Prospective Diabetes Study is the largest study in Type 2 diabetes with pre-specified renal outcomes. The study showed that the natural history of nephropathy in newly diagnosed Type 2 diabetic patients was similar to that described previously in those with Type 1 diabetes. Around 2% per annum progress from normo- to micro-albuminuria [urinary albumin concentration (UAC) > 50 mg/l] and a further 2% from microalbuminuria to clinical grade proteinuria (UAC > 300 mg/l). Mortality rates for those with nephropathy are high, increasing from 1.4% per annum (normoalbuminuria) to 4.6% per annum (clinical grade proteinuria), and to 19.2% per annum for those with renal impairment. More intensive blood glucose control resulted in both a 33% reduction in relative risk of development of microalbuminuria or clinical grade proteinuria at 12 years, and a significant reduction in the proportion doubling their plasma creatinine (0.91 vs. 3.52%, P = 0.0028). Tighter blood pressure control also reduced microalbuminuria and clinical grade proteinuria; but at 6 years there was no effect on plasma creatinine levels. These data underline the importance of glycaemic and blood pressure control in Type 2 diabetes in order to prevent diabetic nephropathy. Those patients unlucky enough to develop nephropathy need intensive surveillance and correction of cardiovascular risk factors.

Prevalence and risk factors for diabetic neuropathy in an urban south Indian population: the Chennai Urban Rural Epidemiology Study (CURES-55).

Abstract: Aims This study was conducted to determine the prevalence of, and risk factors for, diabetic neuropathy (DN) in south Indian Type 2 diabetic subjects. Methods Subjects were recruited from the Chennai Urban Rural Epidemiology Study, conducted on a representative cohort from Chennai city. A total of 1629 diabetic subjects were included, of whom 1291 were known to have diabetes (KD) subjects and 338 were randomly selected newly detected diabetic (NDD) subjects. Neuropathy was diagnosed if vibratory perception threshold at the great toe, measured by biothesiometry, exceeded mean + 2 sd of a healthy non-diabetic study population aged 20–45 years (cut point ≥ 20 V). Results The overall prevalence of DN was 26.1% (age-adjusted 13.1%) with no significant difference in gender. The prevalence of neuropathy was significantly higher in KD subjects compared with NDD subjects (27.8 vs. 19.5%, P = 0.002). The prevalence of diabetic retinopathy (24.1 vs. 15.3%, P 15 years compared with ≤ 5 years was 5.7 (95% confidence interval: 3.52–9.08, P < 0.0001). Regression analysis showed age (P < 0.0001), glycated haemoglobin (P = 0.001) and duration of diabetes (P = 0.045) to be significantly associated with neuropathy. Conclusions This cross-sectional population-based study shows that, among urban south Indian Type 2 diabetic subjects, the prevalence of DN is 26.1% and that DN is significantly associated with age, glycated haemoglobin and duration of diabetes.

Outcomes of pregnancies in women with pre-gestational diabetes mellitus and gestational diabetes mellitus; a population-based study in New South Wales, Australia, 1998-2002.

Abstract: Aim To determine population-based rates and outcomes of pre-gestational diabetes mellitus (pre-GDM) and gestational diabetes mellitus (GDM) in pregnancy. Methods This was a cross-sectional study, using linked population databases, of all women, and their infants, discharged from hospital following birth in New South Wales (NSW) between 1 July 1998 and 31 December 2002. Women with, and infants exposed to pre-GDM or GDM were compared with those without diabetes mellitus for pregnancy characteristics and outcomes. Results Women with a singleton pregnancy (n = 370 703) and their infants were included: 1248 women (0.3%) had pre-GDM and 17 128 (4.5%) had GDM. Of those women with pre-GDM, 57% had Type 1 diabetes, 20% had Type 2 diabetes and for 23% the type of diabetes was unknown. Major maternal morbidity or mortality was more common in women with pre-GDM (7.9%) [odds ratio (OR) 3.2, 95% confidence interval (CI) 2.6, 3.9] and in women with GDM (3.1%) (OR 1.2, 95% CI 1.1, 1.4) when compared with women without diabetes (2.6%). Major infant morbidity or mortality occurred more frequently in infants exposed to pre-GDM compared with no diabetes (13.6% vs. 3.1%) (OR 5.0, 95% CI 4.2, 5.8) and in infants exposed to GDM compared with no diabetes (3.2% vs. 2.3%) (OR 1.4, 95% CI 1.3, 1.5). Conclusions Pre-GDM and GDM continue to be associated with an increased risk of adverse maternal and neonatal outcomes; however, women with GDM have adverse outcomes less frequently. Rates of GDM and pre-GDM appear to be increasing over time. Clinicians should consider the potential for adverse outcomes, and arrange referral to appropriate services.

Impact of 3-year lifestyle intervention on postprandial glucose metabolism: the SLIM study

Abstract: Objective To determine the effect of a 3-year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT). Methods The study was a randomized controlled lifestyle intervention over 3 years. A total of 147 IGT subjects (75 male, 72 female) were randomized to the intervention (INT) group or control (CON) group; 106 subjects (52 INT, 54 CON) completed 3 years of intervention. Annually, glucose, insulin and free fatty acid (FFA) concentrations were determined fasting and after an oral glucose tolerance test. Measurements of body weight, serum lipids, blood pressure and maximal aerobic capacity were also performed. Results Analysis of those who completed the 3-year trial, showed that the lifestyle intervention improved body weight (INT -1.08 +/- 4.30 kg; CON +0.16 +/- 4.91 kg, P = 0.01), homeostatis model assessment index for insulin resistance and 2-h FFA. Two-hour glucose concentrations improved in the INT group, the difference being most pronounced after 1 year, with a return to baseline values after 3 years, from 8.59 +/- 1.55 to 8.55 +/- 0.34 mM; in contrast, 2-h glucose deteriorated in the CON group-from 8.46 +/- 1.84 to 9.35 +/- 2.50 mM (P = 0.02). In the INT group, diabetes incidence was reduced by 58% (P = 0.025). Conclusion Our lifestyle intervention showed a sustained beneficial effect on 2-h glucose concentrations, insulin resistance and 2-h FFA, even after 3 years. Our lifestyle intervention is effective, but for implementation more information is needed about factors influencing adherence.

Diabetes and anxiety in US adults: findings from the 2006 Behavioral Risk Factor Surveillance System

Abstract: Aims Anxiety disorders may cause substantial impairment in patient functioning and well-being. Little is known about the relationship between diabetes and anxiety. We estimated the prevalence of lifetime diagnosis of anxiety in adults aged ≥ 18 years with and without diabetes in the USA. Methods We analysed data from the 2006 Behavioral Risk Factor Surveillance System (total, N = 201 575; 20 142 with diabetes; 39.4% men, 77.9% non-Hispanic Whites, 8.1% non-Hispanic Blacks and 7.7% Hispanics; mean age 52.4 years). Diabetes and lifetime diagnosis of anxiety were self-reported. A multivariable log–binomial model was used to estimate prevalence ratios (PR) and associated 95% confidence intervals (CI) of anxiety based on diabetes status. Results The overall age-adjusted prevalence of lifetime diagnosis of anxiety was 19.5 and 10.9% in people with and without diabetes, respectively. After adjustment for educational level, marital status, employment status, current smoking, leisure-time physical activity and body mass index, people with diabetes had a 20% higher prevalence of lifetime diagnosis of anxiety than those without (PR 1.20; 95% CI 1.12, 1.30). There were no significant differences in the PR by gender (P = 0.06). However, the ratios differed significantly by age (P = 0.04) and by race/ethnicity (P < 0.01), indicating that people aged 18−29 years (PR 1.70; 95% CI 1.19, 2.43) and Hispanics (PR 1.69; 95% CI 1.33, 2.15) had a higher ratio than their counterparts. Conclusion Diabetes was significantly associated with anxiety in adults in this large population-based sample, particularly in Hispanics and young adults.

Long-term efficacy and safety of insulin detemir compared to Neutral Protamine Hagedorn insulin in patients with Type 1 diabetes using a treat-to-target basal–bolus regimen with insulin aspart at meals: a 2-year, randomized, controlled trial

Abstract: Aims: This 24-month, multi-national, open-label, parallel group trial investigated the long-term efficacy and safety of insulin detemir and Neutral Protamine Hagedorn insulin in combination with mealtime insulin aspart in patients with Type 1 diabetes using a treat-to-target concept. Methods: Patients were randomized 2 : 1 to detemir (n = 331) or NPH (n = 166) groups. Basal insulin was initiated once daily (evening) and titrated individually based on self-measured plasma glucose (PG) levels, aiming for pre-breakfast and pre-dinner targets ≤ 6.0 mmol/l. A second basal morning dose could be added according to pre-defined criteria. Results: After 24 months, superiority of glycated haemoglobin (HbA) was achieved with detemir compared to NPH (detemir 7.36%, NPH 7.58%, mean difference -0.22% points) [95% confidence interval (CI) -0.41 to -0.03%], with reductions of 0.94% and 0.72% points, respectively. Fasting PG (FPG) was also lower with detemir (detemir 8.35 mmol/l, NPH 9.43 mmol/l; P = 0.019). Twenty-two per cent of patients treated with detemir reached an HbA ≤ 7.0% in the absence of confirmed hypoglycaemia during the last month of treatment vs. 13% on NPH (P = 0.019). Risk of major and nocturnal hypoglycaemia was 69% and 46% lower with detemir than with NPH (P < 0.001), respectively; patients treated with detemir gained less weight (detemir 1.7 kg, NPH 2.7 kg; P = 0.024). The overall safety profile was similar in the two groups and treatment with detemir did not result in any unexpected findings. Conclusions: Long-term treatment with the insulin analogues detemir + aspart was superior to NPH + aspart in reducing HbA, with added benefits of less major and nocturnal hypoglycaemia and less weight gain.

In Type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine

Abstract: Aims The superiority of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) with glargine is uncertain. In this randomized cross-over study, we compared CSII and MDI with glargine in patients with Type 1 diabetes well controlled with CSII. The primary end-point was glucose variability. Methods Thirty-nine patients [38.1 ± 9.3 years old (mean ± sd), diabetes duration 16.6 ± 8.2 years, glycated haemoglobin (HbA1c) 7.6 ± 0.8%], already on CSII for at least 6 months, were randomly assigned to CSII with lispro or MDI with lispro and glargine. After 4 months they were switched to the alternative treatment. During the last month of each treatment blood glucose variability was analysed using glucose standard deviation, mean amplitude of glycaemic excursions (MAGE), lability index and average daily risk range (ADRR). As secondary end-points we analysed blood glucose profile, HbA1c, number of episodes of hypo- and hyperglycaemia, lipid profile, free fatty acids (FFA), growth hormone and treatment satisfaction. Results During CSII, glucose variability was 5–12% lower than during MDI with glargine. The difference was significant only before breakfast considering glucose standard deviation (P = 0.011), significant overall using MAGE (P = 0.016) and lability index (P = 0.005) and not significant using ADRR. Although HbA1c was similar during both treatments, during CSII blood glucose levels were significantly lower, hyperglycaemic episodes were fewer, daily insulin dose was less, FFA were lower and treatment satisfaction was greater than during MDI with glargine. The frequency of hypoglycaemic episodes was similar during both treatments. Conclusions During CSII, glucose variability is lower, glycaemic control better and treatment satisfaction higher than during MDI with glargine.

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes.

Abstract: Aim To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose-lowering drugs. Methods Thirty Type 2 diabetic subjects (16 males and 14 females; mean age 65 ± 1 years) who were taking oral glucose-lowering medication regularly were enrolled in this randomized, placebo-controlled, double-blind study. Changes in lipid profiles, oxidized low-density lipoprotein (ox-LDL), glycaemic control, components of the metabolic syndrome, C-reactive protein (CRP) and urinary albumin excretion (UAE) were assessed after cranberry or placebo treatment for 12 weeks. Results Low-density lipoprotein (LDL) cholesterol decreased significantly in the cranberry group (from 3.3 ± 0.2 to 2.9 ± 0.2 mmol/l, P = 0.005) and the decrease was significantly greater than that in the placebo group (–0.4 ± 0.1 vs. 0.2 ± 0.1 mmol/l, P < 0.001). Total cholesterol and total : high-density lipoprotein (HDL) cholesterol ratio also decreased significantly (P = 0.020 and 0.044, respectively) in the cranberry group and the reductions were significantly different from those in the placebo group (P < 0.001 and P = 0.032, respectively). However, ox-LDL levels did not change significantly in response to cranberry consumption. Neither fasting glucose nor glycated haemoglobin improved in either group. Changes in components of the metabolic syndrome, UAE and CRP were not significantly different between groups. Conclusions Cranberry supplements are effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol and total cholesterol levels, as well as total : HDL cholesterol ratio, and have a neutral effect on glycaemic control in Type 2 diabetic subjects taking oral glucose-lowering agents.

Chronic administration of Sildenafil improves markers of endothelial function in men with Type 2 diabetes.

Abstract: Objective Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors. The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2). Methods In a double-blind, placebo-controlled parallel design, 20 patients without erectile dysfunction randomly received a loading dose of sildenafil (100 mg) for 3 days, followed by either sildenafil 25 mg three times a day (t.d.s.) for 4 weeks or sildenafil 25 mg t.d.s. for 4 days followed by placebo t.d.s. for 3 weeks. Results After 1 week, flow-mediated dilatation (FMD) improved significantly (> 50% compared with baseline) in patients allocated to both sildenafil arms (62 and 64%, respectively). In patients allocated to chronic sildenafil, a progressive increase in percentage of patients with FMD improvement was noted (78, 86 and 94% at 2, 3 and 4 weeks, respectively) while a progressive decrease in the placebo group occurred (45, 18 and 6% at 2, 3 and 4 weeks, respectively). At the end of the study, a significant improvement in FMD compared with baseline was noted after chronic sildenafil (FMD from 6.8 ± 0.5 to 12.5 ± 0.7%, P = 0.01 vs. baseline). A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil; significant changes from baseline in C-reactive protein, interleukin 6, intercellular adhesion molecule and vascular adhesion molecule levels were also found. Conclusions In DM2 patients, daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation, suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition. Diabet. Med. 25, 37–44 (2008)

Prevalence and associations of psychological distress in young adults with Type 1 diabetes

Abstract: AIMS To determine the prevalence of psychological distress in young adults with Type 1 diabetes and to explore associated factors. METHODS Ninety-two participants with Type 1 diabetes (46 male, 46 female) attending a young adult clinic completed two psychological self-report assessments; the Centre for Epidemiological Studies-Depression Scale (CES-D) and Adult Self-Report Scale (ASR). The mean age was 21.6 +/- 2.8 years (sd) and mean duration of diabetes was 9.3 +/- 5.4 years. A questionnaire identified the method of insulin delivery, the frequency of blood glucose monitoring and hypoglycaemia requiring third-party assistance. HbA(1c) was measured. RESULTS Of the participants, 35.2% reported depressive symptoms (CES-D > or = 16), 23.1% indicating severe depressive symptoms (CES-D > or = 24), and 32.2, 40.4 and 35.5% of participants reported significant distress (ASR > or = 60) on the ASR total problem scales, ASR internalizing and ASR externalizing scores, respectively. Mean HbA(1c) levels were higher in participants with depressive symptoms compared with those with normal scores (CES-D > or = 16, HbA(1c)= 9.4% vs. CES-D < 16, HbA(1c)= 8.4%, P = 0.01). Factors associated with psychological distress included use of continuous subcutaneous insulin infusion (CSII) (P = 0.02) and increased frequency of hypoglycaemic episodes (P = 0.03). CSII users had higher CES-D (21.3 vs. 11.9, P = 0.001) and ASR-Total (59.7 vs. 53.0, P = 0.02) scores than non-CSII users. CONCLUSIONS Approximately one-third of young adults with Type 1 diabetes experience psychological distress, which is associated with poorer glycaemic control. Psychological distress was related to frequency of hypoglycaemic episodes and method of insulin administration, with significantly greater distress being observed in those using CSII. These findings support inclusion of a psychologist in the diabetes team.

Compliance with physical activity recommendations in US adults with diabetes.

Abstract: Aims To investigate whether US adults with diabetes meet both the national and American Diabetes Association (ADA) recommendations for physical activity compared with people without diabetes, and to examine the trends of this behaviour over time. Methods We analysed data from large nationally representative cohorts from the 1996–2005 Behavioral Risk Factor Surveillance System. The number of participants ranged from 98 127 in 1996 to 204 977 in 2005, and the number of people with diabetes ranged from 4379 in 1996 to 13 608 in 2005. Participants were classified by their exercise status and physical activity levels. The age-standardized prevalence of physical activity participation or meeting physical activity recommendations was calculated in people with and without diabetes. Results People with diabetes participated less in physical activity (63.1–68.9 vs. 71.7–78.3%) and met physical activity recommendations less than people without diabetes (40.2–42.9 vs. 48.0–51.5% for meeting national recommendations and 38.5–41.7 vs. 46.6–49.8% for meeting ADA recommendations). The percentage of people with diabetes who participated in physical activity in the past 10 years or met physical activity recommendations in the past 5 years did not vary, whereas significantly increasing trends were observed in people without diabetes. The odds for adults with diabetes meeting physical activity recommendations were significantly lower than in adults without diabetes even after multivariate adjustment. Conclusion People with diabetes were less likely to meet either national or ADA recommendations for physical activity than people without diabetes. Our results demonstrate the need for more efforts from health-care professionals to promote physical activity in people with diabetes.

Differences in height explain gender differences in the response to the oral glucose tolerance test- the AusDiab study.

Abstract: Aim To determine the extent of gender-related differences in the prevalence of glucose intolerance for the Australian population and whether body size may explain such differences. Methods Cross-sectional data were collected from a national cohort of 11 247 Australians aged ≥ 25 years. Glucose tolerance status was assessed according to both fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) levels following a 75-g oral glucose tolerance test (OGTT). Anthropometric and glycated haemoglobin measurements were also made. Results Undiagnosed diabetes and non-diabetic glucose abnormalities were more prevalent among men than women when based only on the FPG results (diabetes: men 2.2%, women 1.6%, P = 0.02; impaired fasting glycaemia: men 12.3%, women 6.6%, P P = 0.14). Women had a mean FPG 0.3 mmol/l lower than men ( P P = 0.002) and FPG-2hPG increment 0.5 mmol/l greater ( P Conclusions Men and women had different glycaemic profiles; women had higher mean 2hPG levels, despite lower fasting levels. It appeared that the higher 2hPG levels for women related to lesser height and may be a consequence of using a fixed glucose load in the OGTT, irrespective of body size.