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Glucose Profiles (glucose + profile)
Kinds of Glucose Profiles Selected AbstractsAn exploratory study of the effect of using high-mix biphasic insulin aspart in people with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 7 2009U. Dashora Objective:, To compare blood glucose control when using biphasic insulin aspart (BIAsp) three times a day (using 70/30 high-mix before breakfast and lunch), with biphasic human insulin (BHI, 30/70) twice daily in adults with type 2 diabetes already treated with insulin. Research design and methods:, In a 60-day, open-label, crossover study, people with insulin-treated type 2 diabetes [n = 38, baseline haemoglobin A1c 8.3 ± 0.9 (s.d.) %] were randomized to BIAsp three times a day before meals, as BIAsp 70 (70% insulin aspart and 30% protamine-complexed insulin aspart) before breakfast and lunch and BIAsp 30 (30/70 free and protamine-complexed insulin aspart) before dinner, or to human premix insulin (BHI) 30/70 twice a day before meals. A 24-h in-patient plasma glucose profile was performed at the end of each 30-day treatment period. The total daily insulin dose of BIAsp regimen was 110% of BHI and the doses were not changed during the study. Results:, There was no difference between BIAsp and BHI in geometric weighted average serum glucose over 24 h [7.3 vs. 7.7 mmol/l, BIAsp/BHI ratio 0.95 (95% CI 0.88,1.02), not significant (NS)], but daytime geometric weighted average glucose concentration was significantly lower with the BIAsp regimen than with BHI [8.3 vs. 9.2 mmol/l, BIAsp/BHI ratio 0.90 (0.84,0.98), p = 0.014]. The mealtime serum glucose excursion was also lower with BIAsp than with BHI with statistically significant differences at lunchtime [difference ,4.9 (,7.0 to ,2.7) mmol/l, p = 0.000); the difference in glucose excursions above 7.0 mmol/l was also significant [,5.8 (,8.3 to ,3.2) mmol/l, p = 0.000). The proportion of participants experiencing confirmed hypoglycaemic episodes was similar between regimens (42 vs. 43%, NS). Conclusions:, An insulin regimen using high-mix BIAsp (BIAsp 70) before breakfast and lunch and BIAsp 30 before dinner can achieve lower blood glucose levels during the day through reduced mealtime glucose excursions in particular at lunchtime than a twice-daily premix regimen. [source] A method for assessing quality of control from glucose profilesDIABETIC MEDICINE, Issue 7 2007N. R. Hill Abstract Aim As the practice of multiple assessments of glucose concentration throughout the day increases for people with diabetes, there is a need for an assessment of glycaemic control weighted for the clinical risks of both hypoglycaemia and hyperglycaemia. Methods We have developed a methodology to report the degree of risk which a glycaemic profile represents. Fifty diabetes professionals assigned risk values to a range of 40 blood glucose concentrations. Their responses were summarised and a generic function of glycaemic risk was derived. This function was applied to patient glucose profiles to generate an integrated risk score termed the Glycaemic Risk Assessment Diabetes Equation (GRADE). The GRADE score was then reported by use of the mean value and the relative percent contribution to the weighted risk score from the hypoglycaemic, euglycaemic, hyperglycaemic range, respectively, e.g. GRADE (hypoglycaemia%, euglycaemia%, hyperglycaemia%). Results The GRADE scores of indicative glucose profiles were as follows: continuous glucose monitoring profile non-diabetic subjects GRADE = 1.1, Type 1 diabetes continuous glucose monitoring GRADE = 8.09 (20%, 8%, 72%), Type 2 diabetes home blood glucose monitoring GRADE = 9.97 (2%, 7%, 91%). Conclusions The GRADE score of a glucose profile summarises the degree of risk associated with a glucose profile. Values < 5 correspond to euglycaemia. The GRADE score is simple to generate from any blood glucose profile and can be used as an adjunct to HbA1c to report the degree of risk associated with glycaemic variability. [source] Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetesDIABETIC MEDICINE, Issue 3 2006S. G. Ashwell Abstract Aims To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen. Methods In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 ± 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile. Results HbA1c was lower with glargine + lispro than with NPH + human insulin [7.5 vs. 8.0%, difference ,0.5 (95% CI ,0.7, ,0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l,1 h,1, P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l,1 h,1, P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l,1 h,1, P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001). Conclusions Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia. [source] Plasma anhydro- d -glucitol (1,5-AG) as an indicator of hyperglycaemic excursions in pregnant women with diabetesDIABETIC MEDICINE, Issue 2 2006M. Dworacka Abstract Aims To evaluate the use of the plasma 1,5-anhydro- d -glucitol (1,5-AG) level as a possible marker for glucose excursions in pregnant women with diabetes. Methods The study group consisted of 55 pregnant women with diabetes (gestational diabetes mellitus,GDM, n = 28 or pre-gestational diabetes mellitus ,PGDM, n = 27), without hepatic or renal insufficiency, gestational age range 5,38 weeks. In each patient, 24-h glucose profile, glycated haemoglobin and 1,5-AG plasma levels were measured. Mean blood glucose (MBG) and M-value (by Schlichtkrull) were calculated. MBG, M-value and maximal daily glycaemia (MxG) were used as indexes of daily glycaemic excursions. Results A significant correlation was found between the 1,5-AG plasma level and MxG [r = (,0.3)] and between the 1,5-AG level and M-value [r = (,0.36)]. There was no association between the 1,5-AG level and gestational age. Multivariate regression analysis, with 24-h glucose profile, gestational age and MxG as independent variables, showed that MxG was the main parameter determining the 1,5-AG plasma level [, = (,0.68)]. The M-value, the coefficient of glucose fluctuations, also determined the 1,5-AG level but with lower statistical power [, = (0.41)]. No statistical differences were found in the group with HbA1c < 6% or > 6% for 1,5-AG and M-value, while MBG was higher in poorly controlled patients (HbA1c > 6%). Conclusions The plasma 1,5-AG level may be a useful marker of daily glucose excursion in pregnant women with diabetes, as an adjunct to HbA1c monitoring. [source] EFFECTS OF AGAR AND PECTIN ON GASTRIC EMPTYING AND POST-PRANDIAL GLYCAEMIC PROFILES IN HEALTHY HUMAN VOLUNTEERSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007Masaki Sanaka SUMMARY 1Dietary fibre, such as pectin, delays gastric emptying and may enhance post-prandial glucose tolerance. Agar, which is high in fibre content, is widely used in the traditional Japanese diet. Although long-term diet therapy with agar decreases fasting plasma glucose levels in diabetes, knowledge is lacking about the acute effects of agar on gastric emptying and the post-prandial glycaemic profiles. The present study was designed to investigate the acute effects of agar. 2Ten healthy male volunteers were studied on three occasions with three different test meals (450 kcal/500 mL): (i) a fibre-free meal; (ii) a meal with 2.0 g agar; or (iii) a meal with 5.2 g pectin. On each occasion, participants underwent a [13C]-acetate breath test along with serial blood sampling. To quantify gastric emptying, the half [13CO2] excretion time () and the time for maximal [13CO2] excretion rate (tlag) were determined. The post-prandial glycaemic response was expressed as an incremental change from the fasting value at each sampling time. Data were analysed using repeated-measures analysis of variance (anova), followed by a post hoc paired Student's t -test with Bonferroni adjustment. 3The time-course for respiratory [13CO2] excretion differed significantly among the three test meals (P = 0.0004, anova). Compared with the control meal, [13CO2] excretion was significantly lower following consumption of the agar meal (between 40 and 105 min post-prandially; P < 0.025, Student's t -test) and the pectin meal (between 40 and 180 min post-prandially; P < 0.025, Student's t -test). Among the three meals, significant differences were found in (P = 0.002, anova) and tlag (P = 0.011, anova). Compared with the control meal, the agar and pectin meals exhibited a significantly prolonged (P = 0.007 and P < 0.0001, respectively, Student's t -test) and tlag (P = 0.006 and P = 0.002, respectively, Student's t -test). Neither the agar nor pectin meal affected the post-prandial glucose profile. 4In healthy adults, agar and pectin delay gastric emptying but have no impact on the post-prandial glucose response. [source] Hypoglycaemia after pancreas transplantation: usefulness of a continuous glucose monitoring systemCLINICAL TRANSPLANTATION, Issue 6 2003Enric Esmatjes Abstract: Background: After pancreas transplantation (PTx) some patients report occasional symptoms of hypoglycaemia and at times, serious hypoglycaemia. Continuous blood glucose monitoring (CBGM) allows determination of the daily glucose profile and detection of unrecognized hypoglycaemia. The aims of our study were to determine the incidence of hypoglycaemia in PTx and evaluate whether the use of CBGM helps to detect unrecognized nocturnal hypoglycaemia. Patients and methods: We studied 12 patients (six males) with normal functioning PTx and kidney transplantation for more than 3 yr, with systemic drainage of endocrine secretion and stable immunosuppression. A 24-h CBGM using a microdialysis technique (GlucoDay, A. Menarini Diagnostics, Florence, Italy) was performed in all the patients. Results: Three patients had asymptomatic recorded glucose levels below 3.3 nmol/L during the nocturnal period (01:00,07:00 hours) with the glucose levels during these episodes being 2.6, 2.5 and 2.5 nmol/L, and the duration of nocturnal hypoglycaemia being 27, 62 and 93 min, respectively, rising spontaneously without intervention. Patients with hypoglycaemia presented lower glycosylated haemoglobin levels when compared with those not presenting hypoglycaemic episodes, although basal glucose and insulin levels and insulin antibody titres were similar. In one of the three patients presenting hypoglycaemia CBGM was re-evaluated after including an extra snack at bedtime, with subsequent normalization of the blood glucose profile being observed. Conclusion: Unrecognized nocturnal hypoglycaemia is relatively frequent in patients with PTx and 24-h CBMG may be useful to detect these episodes. [source] The relationship of postprandial glucose to HbA1cDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2004Rüdiger Landgraf Abstract The gold standard for the assessment of the overall glycemic control is the determination of HbA1c. There are, however, insufficient data to determine reliably the relative contribution of fasting and postprandial plasma glucose to HbA1c. Increasing evidence suggests that excessive excursions of postprandial glucose might be important for the development of micro- and macroangiopathic complications. With respect to the treatment options, one important question to be answered is whether premeal, postmeal or fasting plasma glucose, alone or in combination, will be necessary in adjusting the therapy to achieve optimal HbA1c levels while minimizing hypoglycemia. HbA1c is difficult to predict from fasting plasma glucose. There are indications that there is a shift in the relative contribution from postprandial glucose at good to fair HbA1c levels (<7.3% to <9.2%) to fasting plasma glucose at high HbA1c (>9.3%). There is also a better correlation of afternoon and evening plasma glucose with HbA1c than with prebreakfast and prelunch plasma glucose values. Since the definition on how to define postprandial glucose is still a matter of debate and since postprandial glucose depends on the premeal blood glucose level and, on the time of the meal, its size and composition and the therapeutic strategy, the data so far available are inconclusive and the best correlation of HbA1c is with the area under the glucose profiles. Continuous glucose monitoring under daily life conditions will be the key to definitely unravel the relationship among HbA1c and fasting, premeal, postprandial and postabsorptive plasma glucose. Copyright © 2004 John Wiley & Sons, Ltd. [source] Therapy of type 2 diabetes mellitus based on the actions of glucagon-like peptide-1DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2002Jens Juul Holst Abstract GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake, that is, inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety and promotes tissue deposition of ingested glucose by stimulating insulin secretion. Thus, it is an essential incretin hormone. In addition, the hormone has been demonstrated to promote insulin biosynthesis and insulin gene expression and to have trophic effects on the beta cells. The trophic effects include proliferation of existing beta cells, maturation of new cells from duct progenitor cells and inhibition of apoptosis. Furthermore, glucagon secretion is inhibited. Because of these effects, the hormone effectively improves metabolism in patients with type 2 diabetes mellitus. Thus, continuous subcutaneous administration of the peptide for six weeks in patients with rather advanced disease greatly improved glucose profiles and lowered body weight, haemoglobin A1C, and free fatty acids (FFA). In addition, insulin sensitivity doubled and insulin responses to glucose were greatly improved. There were no side effects. Continuous administration is necessary because of rapid degradation by the enzyme dipeptidyl peptidase-IV. Alternative approaches include the use of analogues that are resistant to the actions of the enzyme, as well as inhibitors of the enzyme. Both approaches have shown remarkable efficacy in both experimental and clinical studies. The GLP-1-based therapy of type 2 diabetes, therefore, represents a new and attractive alternative. Copyright © 2002 John Wiley & Sons, Ltd. [source] Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes1DIABETIC MEDICINE, Issue 5 2008T. Parkner Abstract Aims To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid-acting insulin analogue and once daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. Methods Twenty-one patients with Type 2 diabetes treated with oral glucose-lowering agents were randomized in this two-period crossover study to an equivalent 24-h dose of continuous subcutaneous infusion of insulin aspart and subsequently once-daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded. Results On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre-injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra-subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra-subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic-only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period. Conclusions Basal continuous subcutaneous infusion of a rapid-acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once-daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. [source] A method for assessing quality of control from glucose profilesDIABETIC MEDICINE, Issue 7 2007N. R. Hill Abstract Aim As the practice of multiple assessments of glucose concentration throughout the day increases for people with diabetes, there is a need for an assessment of glycaemic control weighted for the clinical risks of both hypoglycaemia and hyperglycaemia. Methods We have developed a methodology to report the degree of risk which a glycaemic profile represents. Fifty diabetes professionals assigned risk values to a range of 40 blood glucose concentrations. Their responses were summarised and a generic function of glycaemic risk was derived. This function was applied to patient glucose profiles to generate an integrated risk score termed the Glycaemic Risk Assessment Diabetes Equation (GRADE). The GRADE score was then reported by use of the mean value and the relative percent contribution to the weighted risk score from the hypoglycaemic, euglycaemic, hyperglycaemic range, respectively, e.g. GRADE (hypoglycaemia%, euglycaemia%, hyperglycaemia%). Results The GRADE scores of indicative glucose profiles were as follows: continuous glucose monitoring profile non-diabetic subjects GRADE = 1.1, Type 1 diabetes continuous glucose monitoring GRADE = 8.09 (20%, 8%, 72%), Type 2 diabetes home blood glucose monitoring GRADE = 9.97 (2%, 7%, 91%). Conclusions The GRADE score of a glucose profile summarises the degree of risk associated with a glucose profile. Values < 5 correspond to euglycaemia. The GRADE score is simple to generate from any blood glucose profile and can be used as an adjunct to HbA1c to report the degree of risk associated with glycaemic variability. [source] Insulin aspart vs. human insulin in the management of long-term blood glucose control in Type 1 diabetes mellitus: a randomized controlled trialDIABETIC MEDICINE, Issue 11 2000P. D. Home SUMMARY Aims To compare the efficacy of insulin aspart, a rapid-acting insulin analogue, with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus. Methods Prospective, multi-centre, randomized, open-labelled, parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1070 adult subjects with Type 1 diabetes. Study patients were randomized 2:1 to insulin aspart or unmodified human insulin before main meals, with NPH-insulin as basal insulin. Main outcome measures were blood glucose control as assessed by HbA1c, eight-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia, and adverse events. Results After 6 months, insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 (95% confidence interval 0.03,0.22) %Hb, P < 0.02. Eight-point blood glucose profiles showed lower post-prandial glucose levels (mean baseline-adjusted ,0.6 to ,1.2 mmol/l, P < 0.01) after all main meals, but higher pre-prandial glucose levels before breakfast and dinner (0.7,0.8 mmol/l, P < 0.01) with insulin aspart. Satisfaction with treatment was significantly better in patients treated with insulin aspart (WHO Diabetes Treatment Satisfaction Questionnaire (DTSQ) baseline-adjusted difference 2.3 (1.2,3.3) points, P < 0.001). The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 (0.59,1.18, NS). Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart (1.3 vs. 3.4% of patients, P < 0.05), as were late post-prandial (4,6 h) events (1.8 vs. 5.0% of patients, P < 0.005). Conclusions These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control, hypoglycaemia, and quality of life, in people with Type 1 diabetes mellitus. [source] Aging per se does not influence postprandial glucose levels in type 2 diabetesGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2005Yumiko Magata Background: It is well known that postprandial glucose increases with aging in non-diabetic subjects. The question we addressed is whether elderly type 2 diabetic patients with definite fasting hyperglycemia (, 126 mg/dL) also display increased postprandial hyperglycemia relative to their younger counterparts. Methods: Diurnal plasma glucose profiles were measured in 162 overt type 2 diabetic patients treated by diet alone (diet group) or with sulfonylureas as monotherapy (SU group). Plasma glucose concentrations were measured at 08.00 hours (before breakfast), 10.00, 12.00 (before lunch), 14.00, 18.00 (before dinner), 20.00, 24.00, 03.00, 06.00 and 08.00 hours the next morning. The postprandial glucose area under the curve (AUC) from 08.00 to 24.00 hours was calculated above the baseline level equal to the 08.00-hours plasma glucose value, and the relationships with clinical variables, including age, were assessed. Results: There were no differences in diurnal plasma glucose profiles between the middle-aged (< 65 years) and elderly (, 65 years) groups either the diet group or the SU group. Univariate analysis showed that the postprandial glucose area under the curve was related to the 08:00-hours plasma glucose value (R = 0.583, P < 0.001) in the diet alone group and to the duration of diabetes (R = 0.220, P < 0.05), SU dose (R = 0.330, P = 0.001) and urine CPR (R = ,0.229, P < 0.05) in the SU group. In multivariate analysis, postprandial glucose area under the curve was only related to 08.00 hours plasma glucose value in the diet group (R2 of the model = 0.340, P < 0.001) and to the SU dose in SU group (R2 of the model = 0.145, P < 0.001). Conclusion: These results suggest that aging, per se, does not influence postprandial glucose levels in overt type 2 diabetic patients. [source] The Effect of Metformin in Overweight Patients with Type 1 Diabetes and Poor Metabolic ControlBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009Iben Brock Jacobsen Double-blinded intervention with 2000 mg metformin or placebo daily in 24 type 1 diabetic patients as adjunct to intensive insulin therapy. Primary endpoint was HbA1c, while secondary endpoints were body weight, frequency of hypoglycaemia, blood pressure, lipids, insulin dosage and self-monitored blood glucose profiles were measured. After 24 weeks, no difference in HbA1c was seen between the metformin and placebo groups (,0.5 ± 0.3 vs. ,0.2 ± 0.2%, P = 0.26. , mean ± S.E.M). Mean diurnal blood glucose profiles showed no statistical significant difference between the groups. The total daily insulin dose (IU) was significantly reduced in the metformin group compared to placebo after 24 weeks (,5.9 ± 2.2 vs. 2.9 ± 1.7, P = 0.004. , mean ± S.E.M). An increase in the frequency of hypoglycaemia was seen in the metformin group (0.7 ± 0.9 vs. 0.3 ± 0.5 events patient,1 week,1, P = 0.005), and a reduction in body weight was found using metformin compared to placebo (,3.0 ± 1.0 vs. 0.8 ± 1.1, P = 0.02. , mean ± S.E.M). Lipids and blood pressure did not differ significantly after intervention. Metformin, as adjunct to intensive insulin therapy, was associated with a reduction in the total daily insulin dose and a significant weight loss in patients with type 1 diabetes mellitus. [source] Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitusBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2009Patricia N. Sidharta WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Urotensin-II (U-II) is one of the most potent vasoconstrictors identified thus far. , Although differences in both U-II blood levels and U-II receptor (UT-receptor) expression have been observed in patients with cardiovascular and cardiorenal disease, the precise function in humans has not been elucidated. , U-II and its receptor have been reported to be involved in glucose metabolism and insulin resistance, which can lead to the development of Type 2 diabetes mellitus. , In rat models of diabetes, palosuran, a selective, potent antagonist of the human UT-receptor, improved several disease markers. WHAT THIS STUDY ADDS , In this study in diabetic patients, the effects of palosuran on insulin secretion and sensitivity were investigated using a hyperglycaemic glucose clamp and a meal tolerance test and daily glucose levels were also studied. , Although no obvious beneficial effect of palosuran in this patient population was observed, the study contributes to providing more insight inro the human U-II/UT-receptor system. AIMS To investigate the effects of palosuran, a nonpeptidic, potent and selective antagonist of the urotensin-II receptor, on insulin and glucose regulation in 20 diet-treated patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, randomized, crossover, proof-of-concept study. METHODS After 4 weeks' oral treatment with 125 mg palosuran or placebo b.i.d., effects on insulin secretion and sensitivity and blood glucose levels were assessed by means of a hyperglycaemic glucose clamp, meal tolerance test, homeostasis model assessment-insulin resistance score, and daily self-monitoring of blood glucose. Plasma concentrations of palosuran were determined for 12 h on the last day of intake. RESULTS Palosuran did not affect second-phase insulin response (primary end-point) during the hyperglycaemic glucose clamp in comparison with placebo [paired difference of ,1.8 µU ml,1, 95% confidence interval (CI) ,7.8, 4.2]. Likewise, no effects of palosuran were detected on the first-phase insulin response, or on insulin secretion and blood glucose levels during the meal tolerance test or on homeostasis model assessment-insulin resistance score. No clinically significant effects on daily blood glucose profiles were observed during the study. Geometric mean Cmax and AUC, (95% CI) and median tmax (range) in this patient population were 180 ng ml,1 (125, 260), 581 ng·h ml,1 (422, 800) and 3.0 h (0.67, 4.3), respectively. CONCLUSIONS The results of this study indicate that antagonism of the urotensin-II system does not influence insulin secretion or sensitivity or daily blood glucose levels in diet-treated patients with Type 2 diabetes. [source] |