Inter- and intra-rater-reliability of a clinical framework for spine-related neck-arm pain.

OBJECTIVE: A mechanism-based clinical framework for spine-related pain differentiates (i) somatic referred pain, ii) heightened nerve mechanosensitivity, iii) radicular pain, iv) radiculopathy and mixed-pain. This study aimed to determine the reliability of proposed framework. METHOD: Fifty-one people with unilateral spine-related neck-arm pain were assessed and categorized by examiner-1. The classifications were compared to those made by two other examiners, based on written documentation of examiner-1. Cohens kappa was calculated between examiner-pairs; Fleiss Kappa among all examiners to assess agreement in classifying subgroups and entire framework. RESULT: Inter-rater-reliability showed moderate to almost perfect reliability (somatic: no variation, mechanosensitivity: 0.96 (95% CI 0.87-1.0) to 1.0 (95% CI: 1.0-1.0), radicular pain: 0.46 (95% CI: 0.19-0.69) to 0.62 (95% CI: 0.42-0.81), radiculopathy: 0.65 (95% CI: 0.43-0.84) to 0.80 (95% CI: 0.63-0.96) mixed-pain: 0.54 (95% CI: 0.21-0.81) to 0.75 (95% CI: 0.48-0.94). There was almost perfect to moderate reliability among all examiners (somatic: no variation, mechanosensitivity: 0.97 (95% CI: 0.82-1.0), radicular pain: 0.56 (95% CI: 0.40-0.71), radiculopathy: 0.74 (95% CI: 0.58-0.90), mixed-pain: 0.63 (95% CI: 0.47-0.79), entire framework: 0.64 (95% CI: 0.57-0.71)). Intra-rater-reliability showed substantial to almost perfect reliability (somatic: no variation, mechanosensitivity: 0.96 (95% CI: 0.87-1.0), radicular pain: 0.76 (95% CI: 0.57-0.92), radiculopathy: 0.84 (95% CI: 0.67-0.96), mixed-pain: 0.83 (95% CI: 0.60-1.0), entire framework: 0.80 (95% CI: 0.61-0.92). CONCLUSION: Moderate to almost perfect reliability in subgrouping people with spine-related neck-arm pain and substantial reliability for entire framework support this classification's reliability.

Low within- and between-day variability in exposure to new insulin glargine 300 U/ml.

AIMS: To characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM). METHODS: A total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability. RESULTS: The cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was <2, and both the swing and peak-to-trough fluctuation were <1. Day-to-day reproducibility of exposure was high: the between-day within-subject coefficients of variation for total systemic exposure (area under the serum insulin glargine concentration time curve from time 0 to 24 h after dosing) and maximum insulin concentration were 17.4% [95% confidence interval (CI) 15-21] and 33.4% (95% CI 28-41), respectively. Reproducibility of the metabolic effect was lower than that of exposure. CONCLUSIONS: Gla-300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use.

Safety, efficacy and weight effect of two 11ß-HSD1 inhibitors in metformin-treated patients with type 2 diabetes.

AIMS: We assessed safety and efficacy of two selective 11ß-HSD1 inhibitors (RO5093151/RO-151 and RO5027383/RO-838) in this randomized, controlled study in metformin-treated patients with type 2 diabetes. METHODS: Patients either received placebo (N = 21), RO-151 BID 5 mg (N = 24) or 200 mg (N = 20) or RO-838 QD 50 mg (N = 21) or 200 mg (N = 24) for 28 days. Metabolic assessments comprising of nine-point plasma glucose profiles, oral glucose tolerance tests and determination of metabolic biomarkers including insulin, C-peptide, glucagon, HbA1c and lipids were done at baseline and end of treatment. RESULTS: Despite the short treatment duration, both RO-151 and RO-838 showed trends for improved HbA1c and consistent reductions in body weight (-0.86 to -1.67 kg) exceeding those observed with placebo (-0.28 kg, p = 0.019 for 200 mg RO-151 vs. placebo). Insulin sensitivity parameters (e.g. HOMA-IR and Matsuda-Index) improved non-significantly with 200 mg RO-151. Lipid parameters did not consistently improve with either compound, but RO-838 led to non-significant increases in triglycerides and VLDL-cholesterol versus placebo. Both compounds were well tolerated and showed inhibitory effects on 11ß-HSD1 activity based on urinary corticosteroid excretion. As reported for other 11ß-HSD1-inhibitors increased concentrations of ACTH and adrenal androgen precursors were found with RO-151, but not with RO-838. CONCLUSIONS: Slight metabolic improvements were seen, in particular with RO-151 high dose, however, the observed changes often did not reach statistical significance and were not clearly dose dependent. Studies of longer duration are needed to further investigate potential benefits and risks of these compounds.

Lixisenatide resensitizes the insulin-secretory response to intravenous glucose challenge in people with type 2 diabetes--a study in both people with type 2 diabetes and healthy subjects.

AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists improve blood glucose control by enhancing glucose-sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo. METHODS: Two single-centre, double-blind, randomized, placebo-controlled, single-dose, crossover studies were performed in healthy subjects (HS) and people with type 2 diabetes mellitus (T2DM). Participants received subcutaneous LIXI or placebo 2 h before an iv glucose challenge. Study endpoints included first- and second-phase insulin response, insulin concentration (INS), glucagon response and glucose disposal rate (K(glucose)). LIXI exposure was measured over 12 h. RESULTS: LIXI 20 µg reached maximum concentration after 2 h and resensitized first-phase insulin secretion by 2.8-fold in T2DM to rates comparable with those in HS on placebo, and raised second-phase insulin secretion by 1.6-fold in T2DM. INS rose correspondingly and glucose disposal was accelerated by 1.8-fold in T2DM. First-phase insulin secretion and glucose disposal were also augmented by LIXI in HS, whereas second-phase insulin secretion reduced blood glucose concentrations to below fasting levels and then ceased, accompanied by a rapid, short-lasting rise in glucagon. Otherwise, suppression of glucagon release subsequent to augmentation of insulin release was unaffected in T2DM and in HS. CONCLUSIONS: LIXI resensitized the insulin response to an iv glucose challenge in people with T2DM, thereby accelerating glucose disposal to nearly physiological intensity, and did not impair counter-regulation to low glucose levels by glucagon.

The once-daily human GLP-1 analogue liraglutide impacts appetite and energy intake in patients with type 2 diabetes after short-term treatment.

The aim was to investigate effects of liraglutide on appetite and energy intake in a randomized, placebo-controlled, double-blind, crossover study. Eighteen subjects with type 2 diabetes were assigned to treatment with once-daily subcutaneous liraglutide (increasing by weekly 0.6 mg increments) or placebo for 3 weeks. Appetite ratings were assessed using visual analogue scales during a 5-h meal test. Energy and macronutrient intake during the subsequent ad libitum lunch were also measured. After 3 weeks, mean postprandial and minimum hunger ratings were significantly lower with liraglutide 1.8 mg than placebo (p < 0.01), and the mean overall appetite score was significantly higher (p = 0.05), indicating reduced appetite. Liraglutide was associated with higher maximum fullness ratings (p = 0.001) and lower minimum ratings of prospective food consumption (p = 0.01). Mean estimated energy intake was 18% lower for liraglutide than placebo [estimated ratio 0.82 (95% CI 0.73;0.94); p = 0.004], but no significant differences in macronutrient distribution were noted. Findings suggest that reduced appetite and energy intake may contribute to liraglutide-induced weight loss.

Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin.

AIM: Assess the pharmacodynamics of lixisenatide once daily (QD) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin. METHODS: In this 28-day, randomized, open-label, parallel-group, multicentre study (NCT01175473), patients (mean HbA1c 7.3%) received subcutaneous lixisenatide QD (10 µg weeks 1-2, then 20 µg; n = 77) or liraglutide QD (0.6 mg week 1, 1.2 mg week 2, then 1.8 mg; n = 71) 30 min before breakfast. Primary endpoint was change in postprandial plasma glucose (PPG) exposure from baseline to day 28 during a breakfast test meal. RESULTS: Lixisenatide reduced PPG significantly more than liraglutide [mean change in AUC(0:30-4:30h) : -12.6 vs. -4.0 h·mmol/L, respectively; p < 0.0001 (0:30 h = start of meal)]. Change in maximum PPG excursion was -3.9 mmol/l vs. -1.4 mmol/l, respectively (p < 0.0001). More lixisenatide-treated patients achieved 2-h PPG <7.8 mmol/l (69% vs. 29%). Changes in fasting plasma glucose were greater with liraglutide (-0.3 vs. -1.3 mmol/l, p < 0.0001). Lixisenatide provided greater decreases in postprandial glucagon (p < 0.05), insulin (p < 0.0001) and C-peptide (p < 0.0001). Mean HbA1c decreased in both treatment groups (from 7.2% to 6.9% with lixisenatide vs. 7.4% to 6.9% with liraglutide) as did body weight (-1.6 kg vs. -2.4 kg, respectively). Overall incidence of adverse events was lower with lixisenatide (55%) versus liraglutide (65%), with no serious events or hypoglycaemia reported. CONCLUSIONS: Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG (AUC) during a morning test meal versus prebreakfast liraglutide. Lixisenatide provided significant decreases in postprandial insulin, C-peptide (vs. an increase with liraglutide) and glucagon, and better gastrointestinal tolerability than liraglutide.

Hyperglycaemia is associated with impaired pulsatile insulin secretion: effect of basal insulin therapy.

AIM: Postprandial insulin pulsatility is impaired in patients with type 2 diabetes, but the effects of exogenous insulin therapy on pulsatile insulin secretion are not known. We addressed, whether pulsatile insulin secretion is related to glycaemic control, whether basal insulin supplementation increases postprandial insulin secretion, and if so, is this accomplished by a specific improvement in pulsatile insulin secretion? METHODS: Fourteen patients with type 2 diabetes underwent a mixed meal test before and after an 8-week treatment period with insulin glargine. Glucose, insulin and C-peptide levels were measured, and insulin pulsatility was determined by deconvolution analysis. RESULTS: Insulin treatment lowered fasting glycaemia from 179.6 ± 7.5 mg/dl to 117.6 ± 6.5 mg/dl (p < 0.001). Postprandial insulin and C-peptide levels increased significantly after the treatment period (p < 0.0001). The total calculated insulin secretion rate increased with insulin treatment (p = 0.0039), with non-significant increases in both pulsatile and non-pulsatile insulin secretion. Insulin pulse frequency was unchanged by the intervention. There was an inverse relationship between fasting and postprandial glycaemia and insulin pulse mass (r(2) = 0.51 and 0.56, respectively), whereas non-pulsatile insulin secretion was unrelated to either fasting or postprandial glucose concentrations (r(2) = 0.0073 and 0.031). CONCLUSIONS: Hyperglycaemia in type 2 diabetes is associated with a reduction in postprandial insulin secretion, specifically through a reduction in insulin pulsatility. Reducing chronic hyperglycaemia by basal insulin therapy enhances endogenous ß-cell function in the postprandial state. These data support the use of basal insulin regimens in the pharmacotherapy of overtly hyperglycaemic patients with type 2 diabetes.

Remogliflozin etabonate, a selective inhibitor of the sodium-dependent transporter 2 reduces serum glucose in type 2 diabetes mellitus patients.

AIMS: Remogliflozin etabonate (RE) is the pro-drug of remogliflozin (R), a selective inhibitor of renal sodium-dependent glucose transporter 2 (SGLT2) that improves glucose control via enhanced urinary glucose excretion (UGE). This study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of RE in subjects with type 2 diabetes mellitus (T2DM). METHODS: In a double-blinded, randomized, placebo-controlled trial, subjects who were drug-naïve or had metformin discontinued received RE [100 mg BID (n = 9), 1000 mg QD (n = 9), 1000 mg BID (n = 9)], or placebo (n = 8) for 12 days. Safety parameters were assessed, including urine studies to evaluate renal function. Plasma concentrations of RE and metabolites were measured with the first dose and at steady state. RE effects on glucose levels were assessed with fasting glucose concentrations, frequently sampled 24-h glucose profiles and oral glucose tolerance tests. RESULTS: No significant laboratory abnormalities or safety events were reported; the most frequent adverse events were headache and flatulence. Plasma exposure to RE and R were proportional to administered dose with negligible accumulation. Mean 24-h UGE increased in RE treatment groups. Compared with the placebo group, 24-h mean (95% CI) changes in plasma glucose were -1.2 (-2.2 to -0.3) (100 mg BID), -0.8 (-1.7 to 0.2) (1000 mg QD) and -1.7 (-2.7 to -0.8) mmol/l (1000 mg BID). CONCLUSIONS: Administration of RE for 12 days is well-tolerated and results in clinically meaningful improvements in plasma glucose, accompanied by changes in body weight and blood pressure in subjects with T2DM.

How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes.

This pedagogical review illustrates the differences between pharmacokinetic (PK) and pharmacodynamic (PD) measures, using insulin therapy as the primary example. The main conclusion is that PD parameters are of greater clinical significance for insulin therapy than PK parameters. The glucose-clamp technique, the optimal method for determining insulin PD, is explained so that the reader can understand the important studies in the literature. Key glucose-clamp studies that compare two basal insulin analogues - insulin glargine and insulin detemir - to Neutral Protamine Hagedorn insulin and to each other are then presented. The review further explains how PD parameters have been translated into useful clinical concepts and simple titration algorithms for everyday clinical practice. Finally, the necessity of overcoming patient and/or physician barriers to insulin therapy and providing continuing education and training is emphasised.

Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study.

AIMS: The study objective was to investigate the safety and tolerability of up-titration to high doses of taspoglutide, a once-weekly human glucagon-like peptide-1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone. METHODS: In this double-blind phase II trial, subjects were randomized to placebo or taspoglutide (20 mg; three separate groups) administered once weekly by subcutaneous injection for 4 weeks. This was followed by dose maintenance at 20 mg, or titration to 30 mg (20/30) or 40 mg (20/40) once weekly with matched placebo for an additional 4 weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up. RESULTS: One hundred and twenty-nine subjects were randomized and treated [mean age 57 years, mean baseline glycated haemoglobin (HbA(1c)), 7.9%]. The most frequently reported AEs were nausea and vomiting. The number of patients reporting gastrointestinal AEs did not increase following titration to higher doses of taspoglutide or when continuing the initial 20 mg regimen. Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses). Although not designed to investigate efficacy, improvement in glycaemic control was observed in all active arms of the study. The proportion of subjects achieving HbA(1c) < 7.0% after 8 weeks of treatment was 72, 53 and 70% in the 20/20-, 20/30- and 20/40-mg arms, respectively, vs. 19% for placebo. CONCLUSIONS: Taspoglutide was safe, well tolerated at high doses and efficacious for lowering HbA(1c). Up-titration of dose was not associated with a worsening AE profile.

Pharmacokinetic and pharmacodynamic properties of taspoglutide, a once-weekly, human GLP-1 analogue, after single-dose administration in patients with Type 2 diabetes.

AIMS: The study objectives were to evaluate the pharmacokinetic and pharmacodynamic properties, as well as safety and tolerability, of single doses of taspoglutide, a human glucagon-like peptide-1 (GLP-1) analogue. METHODS: In a double-blind, placebo-controlled study, 48 patients with Type 2 diabetes [mean age 56 +/- 7 years; mean body mass index (BMI) 30.4 +/- 3.0 kg/m(2)] inadequately controlled with metformin (< or = 2 g/day) were enrolled in three sequential cohorts; 12 patients in each cohort were randomized to a single subcutaneous injection of taspoglutide (1, 8 or 30 mg) and four received placebo. RESULTS: Plasma concentrations peaked within 24 h after injection and were sustained for > or = 14 days with all doses. In comparison with placebo, the 8- and 30-mg doses of taspoglutide significantly reduced glycaemic parameters, including 24-h blood glucose and 5-h postprandial glucose areas under the curve (AUCs), for up to 14 days with the 30-mg dose (P < 0.001). The most common adverse events, primarily gastrointestinal in nature, were dose-dependent and transient. CONCLUSIONS: A single dose of taspoglutide significantly improved glycaemic parameters in Type 2 diabetes patients for up to 14 days. The formulation was well tolerated and appears suitable for weekly administration.

Glucose monitoring by microdialysis: performance in a multicentre study.

AIMS: The aim of this study was to assess the performance of the Continuous Research Tool (CRT) in a multicentre clinical-experimental study. METHODS: Three patient groups totalling 28 subjects with diabetes [group A 10 Type 1 (Ulm), group B 10 Type 1 (Neuss), group C eight Type 2 (Aarhus)] participated in this trial. Two CRT microdialysis probes were inserted in parallel in the abdominal subcutaneous tissue for 120 h in each subject. In subjects in group A, glucose excursions were induced on one study day and those in group B underwent a glucose clamp (eu-, hypo- or hyperglycaemic) on one study day. CRT data were calibrated once with a retrospective calibration model based on a run-in time of 24 h and three blood glucose measurements per day. RESULTS: All analysable experiments, covering a broad range of blood glucose values, yielded highly accurate data for the complete experimental time with a mean relative absolute difference of 12.8 +/- 6.0% and a predictive residual error sum of squares of 15.6 +/- 6.3 (mean +/- SD). Of all measurement results, 98.2% were in zones A and B of the error grid analysis. The average absolute differences were 1.14 mmol/l for Type 1 and 0.88 mmol/l for Type 2 diabetic patients. Relative absolute differences were 16.0% for Type 1 and 12.6% for Type 2 diabetic patients. CONCLUSIONS: These results demonstrate that this microdialysis system allows reliable continuous glucose monitoring in patients with diabetes of either type.

[Interactive thresholded volumetry of abdominal fat using breath-hold t1-weighted magnetic resonance imaging]. / Interaktive Schwellenwert-basierte Volumetrie des abdominalen Fettgehaltes mittels atemgehaltener T1-gewichteter Magnetresonanztomographie.

PURPOSE: Development of a feasible and reliable method for determining abdominal fat using breath-hold T1-weighted magnetic resonance imaging. MATERIALS AND METHODS: The high image contrast of T1-weighted gradient echo MR sequences makes it possible to differentiate between abdominal fat and non-fat tissue. To obtain a high signal-to-noise ratio, the measurements are usually performed using phased array surface coils. Inhomogeneity of the coil sensitivity leads to inhomogeneity of the image intensities. Therefore, to examine the volume of abdominal fat, an automatic algorithm for intensity correction must be implemented. The analysis of the image histogram results in a threshold to separate fat from other tissue. Automatic segmentation using this threshold results directly in the fat volumes. The separation of intraabdominal and subcutaneous fat is performed by interactive selection in a last step. RESULTS: The described correction of inhomogeneity allows for the segmentation of the images using a global threshold. The use of semiautomatic interactive volumetry makes the analysis more subjective. The variance of volumetry between observers was 4.6 %. The mean time for image analysis of a T1-weighted investigation lasted less than 6 minutes. CONCLUSION: The described method facilitates reliable determination of abdominal fat within a reasonable period of time. Using breath-hold MR sequences, the time of examination is less than 5 minutes per patient.

Insulin detemir under steady-state conditions: no accumulation and constant metabolic effect over time with twice daily administration in subjects with Type 1 diabetes.

AIMS: This study investigated the pharmacodynamic and pharmacokinetic characteristics of the novel long-acting insulin analogue insulin detemir (IDet) under single-dose and steady-state conditions in comparison with those of NPH insulin at steady state. METHODS: Twenty-five subjects with Type 1 diabetes [seven females, 18 males, mean age (+/- sd) 39 +/- 12 years, body mass index 24 +/- 3 kg/m(2)] participated in three 24-h glucose clamps. IDet or NPH were given at 12-h intervals in fixed, individualized doses. The first clamp assessed the metabolic effect of NPH at steady state, the second investigated the effect of two single injections of IDet. Subjects continued IDet treatment for 7-14 days, after which the third clamp was performed to investigate IDet at steady state. RESULTS: At steady state, the metabolic effect of IDet was constant over 24 h while a clear peak in the metabolic effect [expressed as glucose infusion rates (GIR)] was observed with NPH after each injection. The fluctuation in the metabolic effect (maximum GIR divided by the average of the GIR values at the interval ends) was significantly lower in the second 12 h of the experiments with IDet under steady-state conditions compared with NPH (fluctuation(12-24 h) 1.27 +/- 0.17 vs. 1.56 +/- 0.72, P < 0.05). The overall metabolic effect of IDet at steady state was comparable with that of NPH [GIR-area under curve (AUC)(0-24 h): 5697 +/- 1861 vs. 5929 +/- 1965 mg/kg] whereas a significantly lower effect (5187 +/- 1784 mg/kg, P = 0.01 vs. steady state) was observed following the first two IDet injections. GIR values at the end of clamp day 2 (first doses) and clamp day 3 (steady state) were comparable [GIR(trough 24 h) 3.7 +/- 1.7 vs. 3.8 +/- 1.6 mg/(kg x min) NS], indicating that IDet had reached steady state after the first two injections. CONCLUSIONS: IDet administered twice daily reached steady state after the second injection and showed a constant metabolic effect over time under steady-state conditions. This should facilitate basal insulin substitution and decrease the risk of hypoglycaemia in insulin-treated subjects.

Inhaled Insulin as alternative delivery system for subjects with diabetes – A literature review

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Application of insulin via the pulmonary route has been investigated since about eighty years, and the first inhaled insulin preparation might be commercially available soon. This review gives a detailed, tabulated overview of the available literature on the safety and efficacy of inhaled insulin in pre-clinical and clinical trials. Data on the time-action profile of inhaled insulin will be presented as-well as the published effects of inhaled insulin on clinical endpoints such as HbA1c, hypoglycemia, and treatment satisfaction. Additionally, the potential risks of inhaled insulin, in particular concerning insulin antibodies and lung function parameters will be discussed. Thus, the aim of this review is to give the reader sufficient details to assess the risk-benefit ratio of inhaled insulin on their own

Dependency of the metabolic effect of sc-injected human regular insulin on intra-abdominal fat in patients with type 2 diabetes.

Ten patients with type 2 diabetes were enrolled in an isoglycemic glucose clamp study to determine the impact of intra-abdominal fat, subcutaneous abdominal fat and total abdominal fat on the metabolic effect of a single bolus (0.2 IU/kg) of sc-injected human regular insulin. The maximum metabolic effect associated highly and negatively with intra-abdominal fat (r = - 0.72, p < 0.02) and with the homeostasis model assessment insulin resistance score (HOMA, r = - 0.71, p < 0.03). Likewise, the total metabolic effect of sc-injected insulin correlated strongly and negatively with intra-abdominal fat (r = - 0.77, p < 0.01), HOMA (r = - 0.74, p < 0.02) and HbA (1c) (r = - 0.70, p < 0.03). Stepwise multiple regression analyses showed that the highest metabolic effect was only significantly predicted by intra-abdominal fat, indicating a high negative correlation with the maximum effect (beta = - 0.72) whereas time to maximum metabolic effect showed a strong (beta = 0.72) and positive correlation with HOMA. In combination with the HOMA, it is intra-abdominal fat, and not subcutaneous abdominal fat, which explains 50 - 75 % of the variability of the effect of sc human regular insulin in patients with type 2 diabetes.

Quantification of total abdominal fat volumes using magnetic resonance imaging.

The purpose of this study was to develop a rapid and reliable method for the measurement of total abdominal fat volumes in diabetic patients using magnetic resonance imaging (MRI). Total volume coverage of the abdomen was obtained using T1-weighted images in 37 diabetic patients (age 48 +/- 13 y mean +/-SD). Quantification of intraabdominal (IAF), subcutaneous (SCF), and total abdominal fat volumes (TAF) was performed using a semiautomated computer assisted analysis. The variability of image analysis for fat measurements between two observers and within observers was assessed. Mean volumes (+/- SD) for IAF, SCF and TAF were 10.5 l (+/- 5.0 l), 15.1 l (+/-7.3 l) and 25.7 l (+/-11.5 l), respectively. Reliability of measurements was excellent for both observers (observer I: intraobserver reliability IAF, SCF and TAF: r = 0.999, r = 0.999 r = 1.0, observer II: r = 0.999, r = 0.999 and r = 1.0), as well as between both observers (interobserver reliability IAF, SCF, and TAF: r = 0.999, r = 0.999, r = 1.0). A single computer analysis required about 9 min in addition to 7 min scan time. The developed analysis method of MR images allows a rapid and reliable determination of total intraabdominal, subcutaneous and total fat volumes. This method has the potential to be very valuable in respective studies in patients with diabetes.