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Biomedical subjects

D R Owens

Publications and source records attributed to D R Owens.

At least 19 recordsLinked to original sources
PubMed2006

Results of the pilot study of DIADEM: a comprehensive disease management programme for type 2 diabetes.

AIMS: The purpose of the study was to evaluate the feasibility and preliminary clinical effects of the DIADEM disease management programme for type 2 diabetic patients. METHODS: The study was performed at two test sites (Cardiff, UK: Aachen, Germany) including 137 and 166 patients, respectively. In 16 study centres any patients with type 2 diabetes capable of communicating by phone and able to perform blood pressure, blood glucose or urine glucose self-measurements were included. The maximum programme duration was 6 months at Cardiff and 4 months at Aachen, during which patients were assessed for glycaemic control, cardiovascular risk profile and the presence of complications of diabetes. Data were entered via the internet to a central server. RESULTS: At entry into the programme the patient group in Cardiff had significantly lower mean age (60.3+/-9.4 years versus 64.9+/-8.7 years, p<0.001) and duration of diabetes (6.1+/-5.7 years versus 7.4+/-7.0 years, p<0.05) than in Aachen, however body mass index (31.6+/-5.2 kg/m(2) versus 29.5+/-4.9 kg/m(2), p<0.01), HbA1c (7.7+/-1.2% versus 7.1+/-1.2%, p<0.001) and systolic blood pressure (138.4+/-15.1 mmHg versus 133.5+/-11.5 mmHg, p<0.001) were significantly higher. In contrast, total cholesterol (4.7+/-1.0 mmol/l versus 5.5+/-1.1 mmol/l, p<0.001) was significantly lower in Cardiff compared to Aachen. Following entry into the programme highly significant improvements in HbA1c (Cardiff from 7.7% to 7.1%, p<0.001; Aachen from 7.2% to 6.8%, p<0.05) and total cholesterol concentrations (Cardiff: 4.66-4.46 mmol/l; Aachen: 5.33-5.15 mmol/l; both p<0.05) were observed. There were no significant changes in blood pressure at either site. CONCLUSIONS: Intensive diabetes care was delivered to DIADEM patients and relevant and significant improvements in diabetes care were achieved demonstrating that an IT-based diabetes disease management service can improve care for patients with type 2 diabetes.

Aged↗
PubMed2006

Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin aspart and insulin glargine in people with type 2 diabetes.

AIMS/HYPOTHESIS: The pharmacokinetic and pharmacodynamic properties of biphasic insulin aspart (BIAsp 30) (30% soluble, 70% protaminated insulin aspart [IAsp]) and insulin glargine (IGlarg) were compared. METHODS: Twelve people with type 2 diabetes took part in two 24-h isoglycaemic clamp studies, 1 week apart. Patients were randomised to treatment with 0.5 U/kg of BIAsp 30 (0.25 U/kg at 08.30 h and 0.25 U/kg at 20.30 h) or 0.50 U/kg IGlarg at 08.30 h. Both insulins were given by subcutaneous injection into the anterior abdominal wall. The plasma glucose, glucose infusion rates, plasma insulin and C-peptide concentrations were measured. RESULTS: All 12 patients were men; mean (+/-SD) age was 58.8 (8.9) years, BMI 31.0 (3.0) kg/m2 and HbA(1c) 7.1 (0.6)%. Plasma glucose was constant throughout the 24-h clamp period. After each injection of BIAsp 30, glucose infusion rates increased, reaching a distinct peak approximately 3-5 h after injection. A much flatter postinjection profile was observed following IGlarg administration. Plasma insulin concentrations rose rapidly after each injection of BIAsp 30, reaching a distinct peak after approximately 2-3 h. A flatter plasma insulin profile reached a plateau approximately 6-16 h after IGlarg administration. Plasma C-peptide fell below baseline after both injections of BIAsp 30 but remained unaltered after IGlarg injection. CONCLUSIONS/INTERPRETATION: The pharmacodynamic and pharmacokinetic profiles were 34 and 28%, respectively, higher following equivalent doses (0.5 U/kg) of BIAsp 30 given as two split doses than following IGlarg given as a single daily dose.

Aged↗
PubMed2006

Relationship between HbA1c and indices of glucose tolerance derived from a standardized meal test in newly diagnosed treatment naive subjects with Type 2 diabetes.

AIMS: To determine the relationship between HbA1c and other indices of glycaemic status derived during a standardized meal tolerance test (MTT) in newly diagnosed treatment-naive subjects with Type 2 diabetes (T2DM). METHODS: T2DM subjects (n = 262) consumed a standard MTT in the morning after a 10-h overnight fast. Frequent samples for plasma glucose (PG) were collected over the 4-h test period. The relationship between HbA1c and other glycaemic indices derived from the MTT were explored. The postprandial glucose exposure was calculated as the area under the incremental plasma glucose curve above the fasting level for the test period (AUC1). Excess hyperglycaemia was calculated as the AUC0-4 h above the arbitrary PG concentrations of 6.0 mmol/l (AUC2) and 5.5 mmol/l (AUC3), respectively [upper limit of fasting normoglycaemia according to World Health Organization (WHO) and American Diabetes Association (ADA), respectively]. Fasting hyperglycaemia was also estimated, being the difference between each of the above and the postprandial excursion. The participants were divided into three subgroups according to HbA1c (Group 1, 9.0%) and the relative contribution calculated of the postprandial glucose and fasting hyperglycaemia to the excess hyperglycaemia above the designated international thresholds for fasting plasma glucose. RESULTS: HbA1c was more strongly correlated with the fasting plasma glucose (r = 0.85, P < 0.001) than the overall postprandial glucose exposure (r = 0.539, P = 0.003). The contribution of fasting hyperglycaemia to excess hyperglycaemia using the WHO criteria for normal fasting plasma glucose for the three groups (Groups 1, 2 and 3) was 50.4%, 54.3% and 69.8%, respectively, and 57.8%, 58.8% and 71.4% using the ADA criteria. CONCLUSIONS: The contribution of fasting hyperglycaemia to excess hyperglycaemia increases as glycaemic control deteriorates, becoming dominant with an HbA1c in excess of 7.0%. These findings indicate which therapeutic approach needs to be adopted based on the HbA1c of the person with T2DM.

Adult↗
PubMed2005

Quality assurance for diabetic retinopathy telescreening.

AIMS: TOSCA was an EU-Commission supported international research project designed to develop telescreening services in diabetic retinopathy and glaucoma. This paper describes the quality assurance methods developed for the diabetic retinopathy telescreening service within the TOSCA project. SETTING: The study was performed in 1895 patients with diabetes between 2000 and 2002 at diabetic retinopathy screening sites in five European countries. Data were analysed centrally. METHODS: Patients attending each clinic's diabetic retinopathy screening service received standardized retinal photography. The images and associated data were transferred electronically to a remote location for grading. Each photographer uploading images and each grader downloading images for assessment was controlled by a systematic quality management approach. The quality assurance measures defined were image quality, intragrader reliability. A cockpit chart was developed for the management and presentation of relevant results and quality measures. For the intragrader reliability tests, 10% of the images were processed for a second grading. An algorithm for calculating differences between repeated gradings was developed. RESULTS: The assessment of image quality for the different sites showed that only 0-0.7% were unassessable. One hundred per cent agreement for both gradings was achieved in 50-85% of graded cases, depending on site and grader, and an agreement better than 95% in 71-100% of cases. CONCLUSIONS: A telemedicine-supported quality assurance process is practical and advantageous. The cockpit charts have proven to be useful tools when monitoring the performance of a telescreening service. Grader feedback showed high satisfaction with the quality assurance process.

Diabetic Retinopathy↗
PubMed2004

A placebo-controlled crossover study comparing the effects of nateglinide and glibenclamide on postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetes.

AIM: This was a randomized, double blind, three period crossover study. The objective was to compare glucose, insulin and C-peptide 24 h profiles in patients with type 2 diabetes mellitus after dosing with nateglinide (given preprandially before three test meals), glibenclamide (administered once before breakfast) or placebo (given before three test meals). METHODS: Fourteen patients underwent screening followed within 3 weeks by three treatment periods of 1 day, each separated by 7 days. Dosing followed a six-sequence balanced, two 3 x 3-replicated Latin square. RESULTS: Mean peak serum insulin levels were lower after nateglinide (115 mU/l) than after glibenclamide (145 mU/l.h; p = 0.017) but higher than after placebo (79 mU/l; p = 0.001). However, peak insulin levels were reached earlier after nateglinide [mean time to peak (tmax) 1.7 h] compared to glibenclamide (mean tmax 2.1 h, p = 0.06). Total insulin exposure over the day was higher after glibenclamide compared with that following nateglinide (1216 vs. 1067 mU/l.h; p = 0.009). Similar findings were seen with serum C-peptide. Despite this, mean peak plasma glucose concentrations were lower following nateglinide (11.4 mmol/l from a baseline of 8.3 mmol/l) compared with glibenclamide (13.2 mmol/l from a baseline of 8.5 mmol/l; p = 0.001) and placebo (14.0 mmol/l from a baseline of 8.0 mmol/L; p < 0.001). CONCLUSIONS: Nateglinide improves early prandial measures of insulin and glucose response to a standard meal, more so than glibenclamide, in people with type 2 diabetes.

Aged↗
PubMed2004

Feasibility of using the TOSCA telescreening procedures for diabetic retinopathy.

AIMS: The TOSCA project was set up to establish a tele-ophthalmology service to screen for diabetic retinopathy (DR) in Europe. The aim of this study was to determine the feasibility of establishing telemedicine-based digital screening for detecting DR and to evaluate the satisfaction of both patients and healthcare professionals with the screening procedures used within the TOSCA project. METHODS: The study was a non-randomized, multicentre study carried out in four different countries over a period of 3 months. Patients (n = 390) with diabetes aged > 12 years were included. Two digital retinal images per eye (macular and nasal) were taken and exported to a central server. Patients were asked to complete a questionnaire to assess satisfaction. Accredited graders carried out grading remotely and the results were reported back to the referring centre. Previously graded patient data chosen randomly to represent examples of both DR and no DR were also sent anonymously to the grading centre at a frequency of approximately every 10 patients. RESULTS: Most (99%) of the images were assessable enabling a retinopathy grade to be assigned to the patient. Patients found the retinal photography procedures acceptable; only 6% in one centre would not recommend the procedure. Healthcare professionals (photographers and graders) were also satisfied with the overall procedures. The average time taken to grade each patient was approximately 5 min. CONCLUSIONS: This study demonstrated that it is feasible to electronically transmit and grade retinal images remotely using the TOSCA process. Built-in quality assurance procedures proved acceptable.

Adolescent↗
PubMed2003

Alternative routes of insulin delivery.

Attempts at replicating physiological insulin secretion, as a means of restoring the normal metabolic milieu and thereby minimizing the risk of diabetic complications, has become an essential feature of insulin treatment. However, despite advances in the production, purification, formulation and methods of delivery of insulin which have occurred in recent years, this has met with limited success. The current advocacy of intensive insulin therapy regimens involving multiple daily subcutaneous injection places a heavy burden of compliance on patients and has prompted interest in developing alternative, less invasive routes of delivery. To date, attempts to exploit the nasal, oral, gastrointestinal and transdermal routes have been mainly unsuccessful. The respiratory tree, with a large surface area, offers the greatest potential for the delivery of polypeptide drugs and there is renewed interest in administrating insulin by the intrapulmonary route. Current pulmonary drug delivery systems include a variety of pressurized metered dose inhalers, dry powder inhalers, nebulizers and aqueous mist inhalers. Recent clinical studies suggest a possible role for inhaled insulin in fulfilling meal-related insulin requirements in persons with Type 1 and Type 2 diabetes. Most experience with inhaled insulin has been obtained using either dry powder formulation in the Nektar Pulmonary Inhaler/Exubera device (Nektar Therapeutics Inc., San Carlos, CA, Aventis, Bridgewater, NJ, Pfizer, NY) or a liquid aerosol formulation in the AERx Insulin Diabetes Management System (Aradigm Corp., Hayward, CA, NovoNordisk A/S, Copenhagen, Denmark). If long-term safety and efficacy is confirmed, inhalation may become the first non-subcutaneous route of insulin administration for widespread clinical use. Despite overwhelming interest and investment in administering insulin via the oral route, success is not expected in the short term. Attempts at utilizing the buccal mucosa and skin are also continuing. Pancreatic transplantation will remain limited to those patients receiving a kidney transplant and immunotherapy. Islet cell transplantation is at an early though encouraging stage following the availability of new less toxic immunosuppressive agents. True insulin independence will require further advances in the combined fields of cell biology and genetics to ensure freedom from both the need for lifelong administration of insulin and the complications of diabetes.

Administration, Buccal↗
PubMed2003

Comparison of the subcutaneous absorption of insulin glargine (Lantus) and NPH insulin in patients with Type 2 diabetes.

The aim of this study was to compare the subcutaneous absorption characteristics of insulin glargine with NPH insulin in patients with Type 2 diabetes. In this single-dose, double-blind, randomized, two-way crossover study, 14 patients with Type 2 diabetes (aged 40-70 years) previously untreated with insulin were randomized to receive in a fasting state either a single subcutaneous injection of 0.3 U/kg 125I-insulin glargine or 0.3 U/kg 125I-NPH insulin. The disappearance of radioactivity was monitored for forty-eight hours. The median time for 25%, 50% and 75% of the radioactivity to disappear from the injection site was significantly longer for insulin glargine compared with NPH insulin (T75% 15.0 and 6.5 h, p=0.009; T50% 26.3 and 13.4 h, p=0.009; T25% 42.4 and 26.6 h, p=0.019, respectively). The mean residual radioactivity remaining at 24, 36 and 48 h after injection remained significantly higher than NPH insulin (54.4 and 27.9%, p=0.0001; 35.0 and 17.0%, p=0.003; 19.2 and 9.2%, p=0.01, respectively). Mean plasma glucose levels reached a minimum after 14.6 and 9 h in response to insulin glargine and NPH insulin, respectively. The subcutaneous absorption of insulin glargine in fasting Type 2 diabetes patients was significantly (2-3 times) slower compared with NPH insulin in patients with Type 2 diabetes. The slower absorption of insulin glargine correlated with the fall in plasma glucose levels over a 24 h period compared with the faster insulin absorption and more rapid decrease in plasma glucose levels observed in response to NPH insulin. Both insulin glargine and NPH insulin were well tolerated.

Adult↗
PubMed2002

Effect of darkness on inner retinal hypoxia in diabetes.

It has been postulated that diabetic retinopathy might be initiated by hypoxia during the hours of darkness. Oscillatory potentials, which reflect inner retinal function, are reduced in diabetic patients. We tested the effect of oxygen inhalation on the amplitude of these oscillatory potentials after dark adaptation in seven patients with type 2 diabetes and eight controls. We found that the decreased oscillatory potentials induced by dark adaptation in the diabetic patients increased during oxygen inhalation to an amplitude that was not significantly different from that of the controls before oxygen. Oscillatory potentials in the controls were unaffected by oxygen. This finding strengthens support for the suggestion that diabetic patients might benefit from sleeping with night-time illumination.

Administration, Inhalation↗
PubMed2002

Perceptions of diabetic retinopathy and screening procedures among diabetic people.

AIMS: To assess how diabetic patients perceive retinopathy, screening for sight-threatening lesions and their own role in preventing blindness. METHODS: A questionnaire was administered to 258 consecutive patients after screening for retinopathy, according to the European Field Guide-Book procedure, in Turin (n = 130) and Wales (n = 128, W). All Welsh patients and 70 in Turin (T1) were on standard diabetes care at their clinic or general practitioner, whereas 60 in Turin (T2) were on permanent group education. RESULTS: According to 65%, 84% and 100% of patients in W, T1 and T2, respectively, diabetes may damage the eyes. Retinopathy had been heard of by 48% (W), 67% (T1) and 100% (T2). In T2, 82% of patients could give a meaningful description of retinopathy but only 17% could use correctly the word 'retina'. In W and T1, 16% and 19% could describe retinopathy but none could describe the retina. In W and T1, 47% and 57% believed they could not help with eye care, whereas 78% in T2 replied that they should control diabetes and 20% that eyes should be checked regularly. Regarding reasons for screening, 100% of patients in T2 answered 'prevention and checks', against 61% in T1 and only 9% in W. In T1 and W, 33% and 37% did not know why they were being screened. CONCLUSIONS: Patients' health perceptions and internal control mechanisms may be insufficiently developed for optimal participation in retinopathy screening. Diabetes care by long-term group education may address this problem.

Aged↗
PubMed2002

Acute effects of valsartan on insulin sensitivity in obese, non-hypertensive subjects with and without type 2 diabetes.

BACKGROUND: Two studies were designed to determine whether a single dose (80 mg) of the angiotensin II receptor blocker (ARB), valsartan, alters insulin sensitivity in obese, non-hypertensive subjects with and without Type 2 diabetes. METHODS: Insulin sensitivity (S(I)), glucose effectiveness (S(G)), and acute insulin response (AIR(0-10 min)) were measured by means of a 3-hour insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT) before and after a single dose of valsartan. Study 1: obese, normotensive non-diabetic male subjects (n = 12), mean (SD) age 37.2 +/- 11.2 years, BMI 32.8 +/- 6.8 kg/m (2); Study 2: obese, normotensive Type 2 diabetic patients (n = 12), mean age 55.7 +/- 6.9 years, BMI 35.0 +/- 6.8 kg/m (2)/l. Both studies were randomised, double-blind, placebo-controlled, single-dose crossover group studies involving subjects in two study days, two weeks apart. After fasting samples were taken, a 300 mg/kg iv glucose bolus was injected at 0 min, and 0.05 U/kg iv insulin was given 20 min later. Blood samples for analysis of glucose and insulin were taken throughout the 3-hour study period. RESULTS: Study 1 (non-diabetic subjects) S(I) 2.81 vs. 2.63 x 10 (-4) min (-1) per microU/ml (p = 0.54), S(G) 0.020 vs. 0.020 min (-1) (p = 0.90), AIR(0-10) min 3305 vs. 3450 microU/min/ml (p = 0.71); Study 2 (patients with type 2 diabetes) S(I) 0.59 vs. 0.85 x 10 (-4) min (-1) per microU/ml (p = 0.15), S(G) 0.013 vs. 0.014 min (-1) (p = 0.71), AIR(0-10) min 65 vs. 119 microU/min/ml (p = 0.14), placebo vs. valsartan, respectively. CONCLUSION: In obese, non-hypertensive non-diabetic and Type 2 diabetic subjects a single dose of valsartan does not alter insulin sensitivity.

Adolescent↗
PubMed2002

Early-phase prandial insulin secretion: its role in the pathogenesis of type 2 diabetes mellitus and its modulation by repaglinide.

The major contributory factor to increasing hyperglycaemia in established Type 2 diabetes mellitus (T2DM) appears to be the progressive delay and attenuation of the prandial insulin response. An important consequence of this derangement is that hepatic glucose production is no longer suppressed during times of prandial glucose intake. Together with a relative impairment in the rate of peripheral glucose disposal, this leads to supra-physiological plasma glucose excursions, which may damage the vasculature. An obvious therapeutic strategy, therefore, would be to increase insulin availability when most needed--in the early prandial phase. In experiments with exogenous insulin interventions, peak post-prandial blood glucose increments were curtailed without undue increases in total insulin exposure. However, available evidence suggests that the sulphonylurea glibenclamide does not effectively alter early-phase prandial insulin release but predominately increases late-phase and basal insulin output, thus incurring the risk of hypoglycaemia. The novel insulin secretagogue repaglinide, by contrast, augments early-phase prandial insulin secretion when taken before meals, as shown by studies in non-diabetic people and patients with newly diagnosed, previously untreated T2DM. Repaglinide exerts its greatest effect on the insulin secretion rate during the first 30 min after a meal is started, thereby going some way to restoring the early insulin secretion curve seen after a meal in non-diabetic people. No residual secretagogue activity is seen 4 hr after taking a single dose of up to 2 mg. Prandial glucose regulation with repaglinide could be associated with lower post-prandial glucose excursions and less risk of post-prandial hypoglycaemia than glibenclamide.

Area Under Curve↗
PubMed2001

Insulins today and beyond.

The advent of insulin almost 80 years ago revolutionised treatment of diabetes and must be one of the most outstanding achievements of twentieth century medicine. Since then, there has been an ever-increasing awareness and acceptance of the need to achieve and sustain near-normoglycaemia to delay onset and retard progression of diabetic angiopathy. Physiological insulin replacement is therefore central to management of patients with diabetes who are unable to make [corrected] insulin. Insulin formulations, treatment strategies, and methods and routes of delivery have changed much, with more and more options for monitoring the effect on blood glucose concentrations. Patients with type 1 and type 2 diabetes need insulin much more aggressively than previously. Parallel developments in glucose-sensing technologies are welcomed as an integral part of safe and optimum implementation of insulin replacement therapy.

Absorption↗
PubMed2001

The influence of plasma glucose upon pulsatile ocular blood flow in subjects with type II diabetes mellitus.

AIMS/HYPOTHESIS: This study investigated the influence of plasma glucose upon pulsatile ocular blood flow in subjects with Type II (non-insulin-dependent) diabetes mellitus. METHODS: A total of 19 subjects with Type II diabetes and 8 normal control subjects undertook a meal tolerance test after an overnight fast. The pulsatile ocular blood flow, using the Ocular Blood Flow Tonometer, and plasma glucose concentrations were taken at times 0 min, 90 min and 240 min. Blood pressure and glycated haemoglobin concentrations, in the subjects with diabetes, were also measured at time 0 min. Pulsatile ocular blood flow and plasma glucose were also measured at times 0 and 90 min in 5 subjects with Type II diabetes mellitus who remained fasting. RESULTS: It was found that the subjects with diabetes who undertook the meal tolerance test showed a significant increase in both plasma glucose concentrations and pulsatile ocular blood flow from time 0-90 min, followed by a decrease from 90 min to the end of the session at 240 min. (p < 0.001 in each case). Regression analysis showed a significant correlation between the change in pulsatile ocular blood flow and the change in plasma glucose concentration (r = 0.671,p = 0.001). Control subjects showed no significant change in either plasma glucose or pulsatile ocular blood flow during the meal tolerance test. Subjects with diabetes mellitus who remained fasting also showed no significant change in pulsatile ocular blood flow or plasma glucose concentrations. No correlation was found between glycated haemoglobin concentrations or blood pressure and pulsatile ocular blood flow. CONCLUSION/INTERPRETATION: Pulsatile ocular blood flow is influenced by changes in plasma glucose concentrations in Type II diabetes mellitus, indicating that uncontrolled hyperglycaemia might result in a higher pulsatile ocular blood flow than might otherwise be expected.

Aged↗
PubMed2001

Relationship between beta-cell responsiveness and fasting plasma glucose in Caucasian subjects with newly presenting type 2 diabetes.

AIMS: beta-cell responsiveness was related to fasting plasma glucose to gain further understanding of pathophysiology of Type 2 diabetes. METHODS: An insulin secretion model gave fasting beta-cell responsiveness M0 (ability of fasting glucose to stimulate beta-cell) and postprandial beta-cell responsiveness MI (ability of postprandial glucose to stimulate beta-cell) by analysing glucose and C-peptide time-concentration curves sampled every 10-30 min over 240 min during a meal tolerance test (MTT; 75 g CHO, 500 kcal). Caucasian subjects with newly presenting Type 2 diabetes according to WHO criteria (N = 83, male/female: 65 : 18, age: 54 +/- 10 years, body mass index (BMI): 30.9 +/- 5.2 kg/m2, fasting plasma glucose (FPG): 11.0 +/- 3.2 mmol/L; mean +/- SD) and Caucasian healthy subjects (N = 54, m/f: 21 : 33, age: 48 +/- 9 years, BMI: 26.1 +/- 3.7 kg/m2, FPG: 5.1 +/- 0.4 mmol/L) were studied. RESULTS: A continuum inverse relationship between MI and FPG was observed. In the diabetes group, MI was closely related to FPG (rs = -0.74, P < 0.0001) and explained 60% intersubject FPG variability with the use of an exponential regression model. CONCLUSIONS: In newly presenting Type 2 diabetes in Caucasian subjects a close inverse association exists between postprandial beta-cell responsiveness and FPG.

Aged↗
PubMed2001

Effects of timing of administration and meal composition on the pharmacokinetic and pharmacodynamic characteristics of the short-acting oral hypoglycemic agent nateglinide in healthy subjects.

These studies examined the influence of timing of administration of nateglinide on the glucose profile and beta-cell secretory response to a standardized test meal and the effect of meal composition on the pharmacokinetic and pharmacodynamic profile. In study 1, nateglinide (60 mg) or placebo was given orally at -10, -1, or +10 min to healthy subjects (n = 12), in relation to a standardized test meal (500 kcal) that commenced at 0 min. In study 2, also in healthy subjects (n = 12), a single oral dose (60 mg) of nateglinide was given either 10 min before or 10 min after the start of each of three different test meals (i.e. high in carbohydrate, fat, or protein). In both studies, the postmeal observation period was a minimum of 240 min. In the first study premeal (-10,-1 min), administration of nateglinide led to earlier and higher peak plasma nateglinide concentrations, compared with postprandial dosing (+10 min). A significantly lower maximum postprandial glucose concentration was seen with preprandial dosing compared with either placebo (P < 0.01) or nateglinide given postprandially (P < 0.01). The impact on the glucose profile was consistent with the enhanced insulin profiles after nateglinide, resulting in higher peak plasma insulin concentrations compared with placebo (P < 0.01). Study 2 confirmed the greater impact of pre- vs. postprandial dosing on the glucose and insulin profiles, irrespective of meal type. Nateglinide administration, before a meal, resulted in a more rapid rise and higher peak nateglinide plasma concentrations, irrespective of meal composition. Preprandial administration of nateglinide was more effective in reducing prandial glucose excursions, compared with postmeal dosing (+10 min), a consequence of the earlier insulin response.

Area Under Curve↗
PubMed2001

Importance of validation of immunoassays for intact proinsulin.

The aim of this study was to compare results obtained from two commercially available immunoassay kits for intact proinsulin. Fasting and post-prandial samples were obtained from both healthy subjects and patients with type 2 diabetes mellitus and assays were carried out according to the manufacturers' instructions. Coefficient of variation of the duplicates in both assays was acceptable with the MLT Intact Proinsulin assay giving slightly better overall precision. Regression analysis indicated a good correlation between the assays (r=0.97), however, a procedure better designed to compare analytical methods demonstrated a considerable lack of agreement for some samples. Dilution of samples in the Dako assay greatly affected the results when compared to samples assayed undiluted, whereas in the MLT assay, dilution of samples produced the expected results. Repeat comparison, assaying samples neat in the MLT assay and diluted 1:5 in the Dako assay, resulted in a considerable improvement in the agreement between the Dako and MLT assays. This study underlines the importance of the use of validation procedures which demonstrate quantitative analytical recoveries from a variety of specimens over the working range of the assay method in question.

Case-Control Studies↗