Management of people with Type 2 diabetes shared between a specialized outpatient clinic and primary health care is noninferior to management in a specialized outpatient clinic: a randomized, noninferiority trial.

AIM: To evaluate whether management of people with Type 2 diabetes shared between a specialized outpatient clinic and primary health care has noninferior HbA1c outcomes compared with mono-sectorial management in a specialized outpatient clinic. METHODS: A randomized controlled, noninferiority study. People with moderate hyperglycaemia, hypertension and/or incipient complications were eligible for the study. All participants had annual comprehensive check-ups at the outpatient clinic. Quarterly check-ups were conducted by general practitioners (GPs) for the shared care group and by endocrinologists at the outpatient clinic for the control group. The primary outcome was the mean difference in HbA1c from baseline to 12 months of follow-up. The noninferiority margin for HbA1c was 4.4 mmol/mol. RESULTS: A total of 140 people were randomized [age 65.0 ± 0.9 years, HbA1c 52 ± 0.8 mmol/mol (6.9 ± 0.1%), systolic BP 135.6 ± 1.1 mmHg; all mean ± sem]. Peripheral neuropathy was present in 68% of participants and microalbuminuria in 19%; 15% had history of a previous major cardiovascular event. Among study completers (n = 133), HbA1c increased by 2.3 mmol/mol (0.2%) in the shared care group and by 1.0 mmol/mol (0.1%) in the control group, with a between-group difference of 1.3 mmol/mol [90% confidence interval (CI) -1.3, 3.9] (0.1%, 90% CI -0.1, 0.4). Noninferiority was confirmed in both per protocol and intention to treat analyses. CONCLUSION: We found that our shared care programme was noninferior to specialized outpatient management in maintaining glycaemic control in this group of people with Type 2 diabetes. Shared care should be considered for the future diabetes management of Type 2 diabetes.

Glucose metabolism in patients with psoriasis.

BACKGROUND: Epidemiological studies strongly suggest that psoriasis predisposes to type 2 diabetes. Several theories have been proposed to explain how these disease entities might be pathophysiologically connected. OBJECTIVES: Our primary objective was to elucidate whether clinical data support the notion of common pathophysiological denominators in patients with psoriasis and type 2 diabetes, and thus to delineate the association between the two conditions that has arisen on the basis of epidemiological studies. METHODS: We reviewed clinical studies investigating parameters of glucose metabolism in patients with psoriasis. The PubMed and Embase databases were searched for studies investigating glucose metabolism in adult patients with psoriasis as a primary or secondary end point. Studies had to include a relevant control group. RESULTS: Twenty-six clinical studies reporting on insulin resistance, glucose tolerance or insulin secretion were eligible for review. The results were widely conflicting, with less than half of the studies showing results suggestive of defective glucose metabolism in patients with psoriasis. In general, the studies suffered from a lack of information regarding possible confounders and patient characteristics. Furthermore, the research methods varied, and in all but one study they might not have been appropriate to detect early and subtle defects in glucose metabolism. CONCLUSIONS: The available literature does not unequivocally support common pathophysiological denominators in psoriasis and type 2 diabetes. Well-designed clinical studies are needed to expose potential diabetogenic defects in the glucose metabolism in patients with psoriasis.

Adaptive changes in pancreas post Roux-en-Y gastric bypass induced weight loss.

BACKGROUND: Obesity has been shown to trigger adaptive increases in pancreas parenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta-cell dysfunction. However, it is not known whether the pancreatic tissue components decrease with weight loss and pancreatic steatosis is reversible following Roux-en-Y gastric bypass (RYGB). Therefore, the objective of the study was to investigate the effects of RYGB-induced weight loss on pancreatic volume and glucose homeostasis. METHODS: Eleven patients were recruited in the Obesity Centre of the University Medical Centre Hamburg-Eppendorf. Before and 6 months after RYGB, total GLP-1 levels were measured during oral glucose tolerance test. To assess changes in visceral adipose tissue and pancreatic volume, MRI was performed. Measures of glucose homeostasis and insulin indices were assessed. Fractional beta-cell area was estimated by correlation with the C-peptide-to-glucose ratio; beta-cell mass was calculated by the product of beta-cell area and pancreas parenchymal weight. RESULTS: Pancreas volume decreased from 83.8 (75.7-92.0) to 70.5 (58.8-82.3) cm3 (mean [95% CI], P = .001). The decrease in total volume was associated with a significant decrease in fat volume. Fasting insulin and C-peptide were lower post RYGB. HOMA-IR levels decreased, whereas insulin sensitivity increased (P = .03). This was consistent with a reduction in the estimated beta-cell area and mass. CONCLUSIONS: Following RYGB, pancreatic volume and steatosis adaptively decreased to "normal" levels with accompanying improvement in glucose homeostasis. Moreover, obesity-driven beta-cell expansion seems to be reversible; however, future studies must define a method to more accurately estimate functional beta-cell mass to increase our understanding of glucose homeostasis after RYGB.

Use of antibiotics in childhood and risk of Type 1 diabetes: a population-based case-control study.

AIMS: To investigate whether the use of antibiotics from infancy to adolescence influences the risk of Type 1 diabetes. METHODS: We conducted a population-based case-control study, including all Type 1 diabetes cases in Denmark among children born between 1997 and 2012 (n = 1578). Odds ratios associating Type 1 diabetes with use of antibiotics were calculated using conditional logistic regression. RESULTS: Overall, we found no association between the use of antibiotics and risk of Type 1 diabetes. Furthermore, no associations were seen specifically for broad-spectrum, narrow-spectrum, bactericidal or bacteriostatic types of antibiotics or for the most frequently used individual classes of antibiotics. No differences were observed in subgroups defined by sex or by age at time of diagnosis. However, filling five or more antibiotic prescriptions in the first 2 years of life specifically was associated with a higher odds ratio of 1.35 (95% CI 1.10-1.64). This association appeared to be driven by exposure to broad-spectrum antibiotics within the second year of life. CONCLUSION: Antibiotic exposure in childhood is generally not associated with the risk of developing Type 1 diabetes. Future studies should investigate the effects of multiple exposures to broad-spectrum antibiotics during the second year of life.

Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes.

AIMS: To investigate the effects of exercise in combination with a glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, or placebo for the treatment of type 2 diabetes. METHODS: Thirty-three overweight, dysregulated and sedentary patients with type 2 diabetes were randomly allocated to 16 weeks of either exercise and liraglutide or exercise and placebo. Both groups had three supervised 60-minute training sessions per week including spinning and resistance training. RESULTS: Glycated haemoglobin (HbA1c) levels dropped by a mean ± standard deviation of 2.0% ± 1.2% (from 8.2% ± 1.4%) in the exercise plus liraglutide group vs 0.3% ± 0.9% (from 8.0% ± 1.2%) in the exercise plus placebo group ( P < .001), and body weight was reduced more with liraglutide (-3.4 ± 2.9 kg vs -1.6 ± 2.3 kg; P < .001). Compared with baseline, similar reductions were seen in body fat (exercise plus liraglutide: -2.5% ± 1.4% [ P < .001]; exercise plus placebo: -2.2% ± 1.9% [ P < .001]) and similar increases were observed in maximum oxygen uptake (exercise plus liraglutide: 0.5 ± 0.5 L O2 /min [ P < .001]; exercise plus placebo: 0.4 ± 0.4 L O2 /min [ P = .002]). Greater reductions in fasting plasma glucose (-3.4 ± 2.3 mM vs -0.3 ± 2.6 mM, P < .001) and systolic blood pressure (-5.4 ± 7.4 mm Hg vs -0.6 ± 11.1 mm Hg, P < .01) were seen with exercise plus liraglutide vs exercise plus placebo. The two groups experienced similar increases in quality of life during the intervention. CONCLUSIONS: In obese patients with type 2 diabetes, exercise combined with GLP-1RA treatment near-normalized HbA1c levels and caused a robust weight loss when compared with placebo. These results suggest that a combination of exercise and GLP-1RA treatment is effective in type 2 diabetes.

No cognitive-enhancing effect of GLP-1 receptor agonism in antipsychotic-treated, obese patients with schizophrenia.

OBJECTIVE: Schizophrenia is associated with profound cognitive and psychosocial impairments. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for diabetes and obesity treatment, and animal studies have indicated cognitive-enhancing effects. In this investigator-initiated, double-blind, randomized, placebo-controlled trial, we tested non-metabolic effects of exenatide once-weekly (Bydureon™) in obese, antipsychotic-treated patients with schizohrenia spectrum disorder. METHOD: Before and after 3 months of exenatide (N = 20) or placebo (N = 20) treatment, patients were assessed with the following: Brief Assessment of Cognition in Schizophrenia (BACS), Rey-Osterreith complex figure test (REY), Short-Form Health Survey (SF-36), Personal and Social Performance Scale (PSP) and the Positive and Negative Syndrome Scale (PANSS). We used BACS composite score as the main outcome measure. RESULTS: Repeated measures analysis of variance on BACS composite score showed significant effect of 'Time' (P < 0.001), no effect of 'Group' (P = 0.64) and no 'Time*Group' interaction (P = 0.77). For REY, SF-36, PSP and PANSS, only significant 'Time' effects were found. CONCLUSION: The non-significant results of this first clinical trial exploring non-metabolic effects of a long-acting GLP-1RA in patients with schizophrenia could reflect a general problem of translating cognitive-enhancing effects of GLP-1RAs from animals to humans or be explained by factors specifically related to schizophrenia spectrum patients with obesity such as antipsychotic treatment.

Impaired beta cell sensitivity to incretins in type 2 diabetes is insufficiently compensated by higher incretin response.

BACKGROUND AND AIMS: The incretin effect is impaired in type 2 diabetes (T2D), but the underlying mechanisms are only partially understood. We investigated the relationships between the time course of the incretin effect and that of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) during oral glucose tolerance tests (OGTTs), thereby estimating incretin sensitivity of the beta cell, and its associated factors. METHODS AND RESULTS: Eight patients with T2D and eight matched subjects with normal glucose tolerance (NGT) received 25, 75, and 125 g OGTTs and corresponding isoglycemic glucose infusions (IIGI). The time course of the incretin effect, representing potentiation of insulin secretion by incretins (PINCR), was determined by mathematical modelling as the time-dependent fold increase in insulin secretion during OGTT compared to IIGI. The time course of PINCR was correlated with that of both GIP and GLP-1 in each subject (median r = 0.67 in NGT and 0.45 in T2D). We calculated an individual beta cell sensitivity to incretins (SINCR) using a weighted average of GIP and GLP-1 (pooled incretin concentration, PIC), as the slope of the relationship between PINCR and PIC. SINCR was reduced in T2D (p < 0.01). In the whole group, mean PIC, GIP and GLP-1 concentrations during the OGTT were inversely correlated with SINCR, but T2D had lower PIC, GIP and GLP-1 levels at the same SINCR (p < 0.05). CONCLUSION: Relative incretin insensitivity is partly compensated for by higher incretin secretory responses. However, T2D shows both impairment in incretin sensitivity and abnormal compensation by incretin secretion.

Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting hyperglucagonaemia.

OBJECTIVE: We evaluated whether patients with histologically verified nonalcoholic fatty liver disease (NAFLD) have an impaired incretin effect and hyperglucagonaemia. METHODS: Four groups matched for age, sex and body mass index were studied: (i) 10 patients with normal glucose tolerance and NAFLD; (ii) 10 patients with type 2 diabetes and NAFLD; (iii) eight patients with type 2 diabetes and no liver disease; and (iv) 10 controls. All participants underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycaemic intravenous glucose infusion (IIGI). We determined the incretin effect by relating the beta cell secretory responses during the OGTT and IIGI. Data are presented as medians (interquartile range), and the groups were compared by using the Kruskal-Wallis test. RESULTS: Controls exhibited a higher incretin effect [55% (43-73%)] compared with the remaining three groups (P < 0.001): 39% (44-71%) in the nondiabetic NAFLD patients, 20% (-5-50%) in NAFLD patients with type 2 diabetes, and 2% (-8-6%) in patients with type 2 diabetes and no liver disease. We found fasting hyperglucagonaemia in NAFLD patients with [7.5 pmol L(-1) (6.8-15 pmol L(-1))] and without diabetes [7.5 pmol L(-1) (5.0-8.0 pmol L(-1))]. Fasting glucagon levels were lower but similar in patients with type 2 diabetes and no liver disease [4.5 pmol L(-1) (3.0-6.0 pmol L(-1))] and controls [3.4 pmol L(-1) (1.8-6.0 pmol L(-1) )]. All groups had similar glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide responses. CONCLUSIONS: Patients with NAFLD have a reduced incretin effect and fasting hyperglucagonaemia, with the latter occurring independently of glucose (in)tolerance.

GLP-1 and Amylin in the Treatment of Obesity.

For decades, extensive research has aimed to clarify the role of pancreas and gut-derived peptide hormones in the regulation of glucose homeostasis and feeding behavior. Among these are the beta-cell hormone amylin and the intestinal L cell hormone glucagon-like peptide-1 (GLP-1). They exhibit distinct and yet several similar physiological actions including suppression of food intake, postprandial glucagon secretion, and gastric emptying-altogether lowering plasma glucose and body weight. These actions have been clinically exploited by the development of amylin and GLP-1 hormone analogs now used for treatment of diabetes and obesity. This review will outline the physiology and pharmacological potential of amylin and GLP-1, respectively, and focus on innovative peptide drug development leading to drugs acting on two or more distinct receptors, such as an amylin and GLP-1 peptide hybrid, potentially producing a more effective treatment strategy to combat the rapidly increasing global obesity.

Effect of antibiotics on gut microbiota, glucose metabolism and body weight regulation: a review of the literature.

Gut bacteria are involved in a number of host metabolic processes and have been implicated in the development of obesity and type 2 diabetes in humans. The use of antibiotics changes the composition of the gut microbiota and there is accumulating evidence from observational studies for an association between exposure to antibiotics and development of obesity and type 2 diabetes. In the present paper, we review human studies examining the effects of antibiotics on body weight regulation and glucose metabolism and discuss whether the observed findings may relate to alterations in the composition and function of the gut microbiota.

Diabetes and obesity treatment based on dual incretin receptor activation: 'twincretins'.

The gut incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted after meal ingestion and work in concert to promote postprandial insulin secretion and regulate glucagon secretion. GLP-1 also slows gastric emptying and suppresses appetite, whereas GIP seems to affect lipid metabolism. The introduction of selective GLP-1 receptor (GLP-1R) agonists for the treatment of type 2 diabetes and obesity has increased the scientific and clinical interest in incretins. Combining the body weight-lowering and glucose-lowering effects of GLP-1 with a more potent improvement of ß cell function through additional GIP action could potentially offer a more effective treatment of diabetes and obesity, with fewer adverse effects than selective GLP-1R agonists; therefore, new drugs designed to co-activate both the GIP receptor (GIPR) and the GLP-1R simultaneously are under development. In the present review, we address advances in the field of GIPR and GLP-1R co-agonism and review in vitro studies, animal studies and human trials involving co-administration of the two incretins, as well as results from a recently developed GIPR/GLP-1R co-agonist, and highlight promising areas and challenges within the field of incretin dual agonists.

Effect of the EndoBarrier Gastrointestinal Liner on obesity and type 2 diabetes: a systematic review and meta-analysis.

Compared with bariatric surgery, less invasive and reversible techniques to counteract obesity and type 2 diabetes (T2D) have been developed, including the EndoBarrier Gastrointestinal Liner [duodenal-jejunal bypass sleeve (DJBS)]. We conducted a systematic review and meta-analyses of eligible trials to evaluate the efficacy and safety of the DJBS. Five randomized controlled trials (RCTs; 235 subjects) and 10 observational studies (211 subjects) were included. The risk of bias was evaluated as high in all studies. The mean body mass index ranged from 30 to 49.2 kg/m(2) and 10-100% of the subjects had T2D. Meta-analysis showed that the DJBS was associated with significant mean differences in body weight and excess weight loss of -5.1 kg [95% confidence interval (CI) -7.3, -3.0; four trials; n = 151; I(2) = 37%] and 12.6% (95% CI 9.0, 16.2; four trials; n = 166; I(2) = 24%), respectively, compared with diet modification. The mean differences in glycated haemoglobin (-0.9%; 95% CI -1.8, 0.0) and fasting plasma glucose (-3.7 mM; 95% CI -8.2, 0.8) among subjects with T2D did not reach statistical significance. Adverse events consisted mainly of abdominal pain, nausea and vomiting. No deaths occurred. Future high-quality long-term RCTs are needed to further assess efficacy and safety.

Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon-like peptide-1 secretion.

AIM: To evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide, glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake. METHODS: On four separate days, nine patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of (i) CDCA, (ii) colesevelam, (iii) CDCA + colesevelam or (iv) placebo. At baseline and for 180 min after instillation, blood was sampled. RESULTS: In both the type 2 diabetes group and the healthy control group, CDCA elicited an increase in GLP-1 levels compared with colesevelam, CDCA + colesevelam and placebo, respectively (p < 0.05). The interventions did not affect plasma glucose, insulin or C-peptide concentrations in any of the groups. CDCA elicited a small increase in plasma insulin : glucose ratio compared with colesevelam, CDCA + colesevelam and placebo in both groups. Compared with colesevelam, CDCA + colesevelam and placebo, respectively, CDCA increased glucagon and delayed gastric emptying in both groups. CONCLUSIONS: CDCA increased GLP-1 and glucagon secretion, and delayed gastric emptying. We speculate that bile acid-induced activation of TGR5 on L cells increases GLP-1 secretion, which, in turn, may result in amplification of glucose-stimulated insulin secretion. Furthermore our data suggest that colesevelam does not have an acute effect on GLP-1 secretion in humans.

Impaired incretin effect is an early sign of glucose dysmetabolism in nondiabetic patients with psoriasis.

BACKGROUND: Patients with psoriasis have an increased risk of type 2 diabetes. The gastrointestinal system plays a major role in normal glucose metabolism, and in healthy individuals, postprandial insulin secretion is largely mediated by the gut incretin hormones. This potentiation is termed the incretin effect and is reduced in type 2 diabetes. The impact of psoriasis on gastrointestinal factors involved in glucose metabolism has not previously been examined. OBJECTIVE: To investigate whether the incretin effect, gastrointestinal-mediated glucose disposal (GIGD) and/or secretion of glucagon and gut incretin hormones are impaired in normal glucose-tolerant patients with psoriasis. METHODS: Oral glucose tolerance tests and intravenous isoglycaemic glucose infusions were performed in 12 patients with moderate-to-severe psoriasis and 12 healthy matched control subjects. RESULTS: In patients with psoriasis, the incretin effect (39% vs. 57%, P = 0.02) and GIGD (53% vs. 61%, P = 0.04) were significantly reduced compared to control subjects. In addition, patients were glucose intolerant and showed exaggerated glucose-dependent insulinotropic polypeptide responses. CONCLUSION: These novel findings support the notion that psoriasis is a prediabetic condition and suggest that gastrointestinal-related mechanisms are involved in the increased susceptibility to type 2 diabetes in patients with psoriasis.

Transfer of liraglutide from blood to cerebrospinal fluid is minimal in patients with type 2 diabetes.

Treatment with liraglutide leads to weight loss. We investigated whether blood-to-cerebrospinal fluid (CSF) transfer of liraglutide occurs, and if so, whether it associates with clinical weight loss following liraglutide treatment in humans. We performed lumbar puncture and blood sampling in eight patients with type 2 diabetes (mean (range)): age 63 (54-79) years; actual body weight: 90 (75-118) kg treated with 1.8 mg liraglutide for 14 (5-22) months and with a treatment-induced weight loss of 8.4 (7-11) kg. We measured liraglutide in plasma and CSF with a radioimmunoassay specific for the N-terminus of the GLP-1 moiety of liraglutide. Mean plasma liraglutide was 31 (range: 21-63) nmol l(-1). The mean CSF-liraglutide concentration was 6.5 (range: 0.9-13.9) pmol l(-1). Ratio of CSF: plasma-liraglutide concentrations was 0.02 (range: 0.07-0.002)% and plasma liraglutide did not correlate with CSF-liraglutide levels (P=0.67). Body weight loss tended to correlate with plasma-liraglutide levels (P=0.06), but not with CSF-liraglutide levels (P=0.69). In conclusion, we measured very low concentrations of liraglutide in CSF, and the levels of CSF liraglutide did not correlate with the actual clinical weight loss in these patients. The amount of liraglutide in plasma tended to correlate with the clinical weight loss.

Sevelamer in a diabetologist's perspective: a phosphate-binding resin with glucose-lowering potential.

Sevelamer is a calcium-free and metal-free phosphate-binding oral drug used in the management of hyperphosphataemia in chronic kidney disease. Preclinical and clinical trials have shown glucose and lipid-lowering effects of sevelamer, thereby giving rise to a potential role of the drug in the treatment of patients with type 2 diabetes. These 'novel' effects are most probably derived from the bile acid-binding properties of sevelamer. The proposed potential is supported by the approval of the bile acid sequestrant colesevelam in the United States for the treatment of type 2 diabetes and hypercholesterolaemia. This article offers a brief review on the effects of sevelamer and a perspective on the potential mechanisms behind the glucose-lowering effect of the drug.

Effects of sitagliptin on counter-regulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double-blind placebo-controlled crossover study.

AIMS: To assess whether the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin affects glucagon and other counter-regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes. METHODS: We conducted a single-centre, randomized, double-blind, placebo-controlled, three-period crossover study. We studied 16 male patients with type 1 diabetes aged 18-52 years, with a diabetes duration of 5-20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction. RESULTS: Sitagliptin treatment significantly increased active levels of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. No significant differences were observed for glucagon or adrenergic counter-regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2-211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8-180) mEq/l; p = 0.008]. CONCLUSIONS: Sitagliptin does not affect glucagon or adrenergic counter-regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia.

Lack of effect of the glucagon-like peptide-1 receptor agonist liraglutide on psoriasis in glucose-tolerant patients--a randomized placebo-controlled trial.

BACKGROUND: It has been proposed that glucagon-like peptide-1 receptor (GLP-1R) agonists used for the treatment of patients with type 2 diabetes might also improve their psoriasis. OBJECTIVE: To assess the efficacy and safety of the GLP-1R agonist liraglutide in glucose-tolerant patients with plaque psoriasis. METHODS: A total of 20 obese (body mass index > 25 kg/m(2)), glucose-tolerant patients with plaque psoriasis (psoriasis area and severity index (PASI) of at least 8) were randomized 1:1 to once-daily subcutaneous injections with liraglutide or placebo for an 8-week period. The primary end points were improvement in PASI and dermatology life quality index (DLQI). Secondary end points included changes in weight and high sensitive C-reactive protein (hsCRP) levels, as well as adverse events. RESULTS: After 8 weeks of treatment, no significant change in PASI was found in the liraglutide group (mean±standard deviation: -2.6 ± 2.1) compared with the placebo group (-1.3 ± 2.4) (P = 0.228). No difference in DLQI was observed between the groups [-2.5 ± 4.4 (liraglutide) vs. -3.7 ± 4.8 (placebo); P = 0.564]. HsCRP did not change in any of the groups (0.26 ± 1 (placebo) vs. 0.25 ± 2.2 (liraglutide); P = 0.992). Liraglutide treatment resulted in a bodyweight loss of 4.7 ± 2.5 kg compared with 1.6 ± 2.7 kg in the placebo group (P = 0.014) accompanied by decreased cholesterol levels. No serious adverse events occurred during the 8-week observation period. The most common complaint was transient nausea, which occurred in 45% of the liraglutide-treated patients but in none from the placebo group. CONCLUSION: Liraglutide treatment for 8 weeks did not significantly change PASI, DLQI, or hsCRP in a small group of glucose-tolerant obese patients with plaque psoriasis compared with placebo. A significant weight loss and decrease in cholesterol levels was observed in liraglutide-treated patients.

Decreased plasma chemerin levels in women with gestational diabetes mellitus.

AIMS: To evaluate fasting and post-prandial serum chemerin levels in pregnant women with and without gestational diabetes, and again following delivery when normal glucose homeostasis is re-established. METHODS: Chemerin levels were measured in serum from nine women with gestational diabetes, and from eight age- and BMI-matched pregnant women with normal glucose tolerance during two meal tests: in the third trimester and 3-4 months post partum. All women with gestational diabetes re-established normal glucose tolerance after delivery. RESULTS: Meal intake did not affect serum chemerin levels. The group with gestational diabetes had lower mean serum chemerin levels during the third trimester compared with the group with normal glucose tolerance (28 ± 1.3 vs. 88 ± 3.5 ng/ml, P < 0.0001). In the group with normal glucose tolerance, mean serum chemerin levels decreased significantly post partum to 57 ± 2.8 ng/ml (P = 0.0001), but remained significantly (P = 0.0003) higher than post-partum levels in the group with gestational diabetes (31 ± 1.9 ng/ml), which did not differ significantly from third trimester levels (P = 0.31). CONCLUSIONS: Normal pregnancy is associated with increased circulating chemerin levels, which may act to reduce pregnancy-induced insulin resistance and prevent glucose intolerance. Women with gestational diabetes, however, have severely reduced chemerin levels that remain low after delivery, which may contribute to the insulin resistance, glucose intolerance and high type 2 diabetes risk associated with gestational diabetes.

Specificity and sensitivity of commercially available assays for glucagon-like peptide-1 (GLP-1): implications for GLP-1 measurements in clinical studies.

AIMS: To evaluate the performances of commercially available glucagon-like peptide-1 (GLP-1) assays and the implications for clinical studies. METHODS: Known concentrations (5-300 pmol/l) of synthetic GLP-1 isoforms (GLP-1 1-36NH2, 7-36NH2, 9-36NH2, 1-37, 7-37 and 9-37) were added to the matrix (assay buffer) supplied with 10 different kits and to human plasma, and recoveries were determined. Assays yielding meaningful results were analysed for precision and sensitivity by repeated analysis and ability to discriminate low concentrations. Endogenous GLP-1 levels in clinical samples were assessed using three commercial kits. RESULTS: The USCN LIFE assay detected none of the GLP-1 isoforms. The active GLP-1 enzyme-linked immunosorbent assays (ELISAs) from Millipore and DRG appeared identical and were specific for intact GLP-1 in buffer and plasma. The Meso Scale Discovery (MSD) total GLP-1 kit detected all six GLP-1 isoforms, although recovery of non-active forms was incomplete, especially in plasma. Millipore total GLP-1 ELISA kit detected all isoforms in buffer, but mainly amidated forms in plasma. The Alpco, Phoenix and Bio-Rad kits detected only amidated GLP-1, but the Alpco kit had a limited measurement range (30 pmol/l), the Phoenix kit had incomplete recovery in plasma and the Bio-Rad kit was insensitive (detection limit in plasma 40 pmol/l). The pattern of postprandial GLP-1 responses in clinical samples was similar between the kits tested, but the absolute concentrations measured varied. CONCLUSIONS: The specificity and sensitivity of commercially available kits for the analysis of GLP-1 levels vary considerably. This should be taken into account when selecting which assay to use and when comparing data from different studies.