Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3.

AIMS: To compare the efficacy and safety of basal insulin peglispro (BIL), which has a flat pharmacokinetic and pharmacodynamic profile and a long duration of action, with insulin glargine (GL) in patients with type 1 diabetes. MATERIALS AND METHODS: In this phase III, 52-week, blinded study, we randomized 1114 adults with type 1 diabetes in a 3 : 2 distribution to receive either BIL (n = 664) or GL (n = 450) at bedtime, with preprandial insulin lispro, using intensive insulin management. The primary objective was to compare glycated haemoglobin (HbA1c) in the groups at 52 weeks, with a non-inferiority margin of 0.4%. RESULTS: At 52 weeks, mean (standard error) HbA1c was 7.38 (0.03)% with BIL and 7.61 (0.04)% with GL {difference -0.22% [95% confidence interval (CI) -0.32, -0.12]; p < 0.001}. At 52 weeks more BIL-treated patients reached HbA1c <7% (35% vs 26%; p < 0.001), the nocturnal hypoglycaemia rate was 47% lower (p < 0.001) and the total hypoglycaemia rate was 11% higher (p = 0.002) than in GL-treated patients, and there was no difference in severe hypoglycaemia rate. Patients receiving BIL lost weight, while those receiving GL gained weight [difference -1.8 kg (95% CI -2.3, -1.3); p < 0.001]. Treatment with BIL compared with GL at 52 weeks was associated with greater increases from baseline in levels of serum triglyceride [difference 0.19 mmol/l (95% CI 0.11, 0.26); p < 0.001] and alanine aminotransferase (ALT) levels [difference 6.5 IU/l (95% CI 4.1, 8.9), p < 0.001], and more frequent injection site reactions. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared with GL for 52 weeks resulted in a lower HbA1c, more patients with HbA1c levels <7%, and reduced nocturnal hypoglycaemia, but more total hypoglycaemia and injection site reactions and higher triglyceride and ALT levels.

Postprandial capillary-venous glucose gradient in Type 1 diabetes: magnitude and clinical associations in a real world setting.

AIMS: To determine the magnitude of the peripheral glucose gradient in patients with Type 1 diabetes in a real world setting and to explore its relationship with insulin dose and macronutrient intake. METHODS: All patients used mealtime analogue insulin. The glucose gradient was assessed using antecubital fossa venous and finger-stick capillary samples, collected concurrently at room temperature. Baseline sampling occurred before the administration of an insulin dose and breakfast of the patient's choosing. Breakfast was consumed an average of 15 min after baseline. The macronutrient content of breakfast was documented. Sampling was repeated 1 and 2 h after baseline. RESULTS: The mean (95% CI) plasma capillary-venous glucose gradient values for 43 patients were: pre-breakfast, 0.21 (0.08-0.34) mmol/l; 1 h after baseline, 0.87 (0.66-1.07) mmol/l; and 2 h after baseline, 0.52 (0.33-0.71) mmol/l. Glucose gradient and dietary carbohydrate intake (g/kg body weight) were positively correlated at both 1 h (P < 0.01) and 2 h after baseline (P < 0.01). No relationship was observed between this gradient and mealtime insulin dose, or the glucose concentration at either time point. CONCLUSIONS: In patients with Type 1 diabetes, a clinically significant glucose gradient is present after the ingestion of a carbohydrate-rich meal. As postprandial capillary and venous plasma glucose concentrations are not equivalent, defining the site of sample collection is important.

Wearing a crotch strap on a correctly fitted lifejacket improves lifejacket performance.

Wearing a lifejacket when immersed in water should support the wearer, maintaining their airway clear of the water. It is proposed that a retention system would improve airway protection by improving retention of the lifejacket around the torso. Study one (n = 10) quantified the performance of lifejackets immediately following a step into water from height when a lifejacket was worn with a crotch strap (two different tightness) and without a crotch strap. Airway freeboard was improved when wearing a crotch strap (P < 0.05) compared with no crotch strap. Study two used a manikin to examine the performance of lifejackets with and without a crotch strap during 3-h exposures to waves. During exposure to waves, the time taken to aspirate the lethal dose of seawater for drowning was doubled when wearing a crotch strap compared with the no-crotch-strap conditions (P < 0.001). Therefore, wearing a crotch strap (functioning retention system) on a correctly fitted lifejacket improves airway protection following accidental immersion and prolonged wave exposure.

The Diabetes Excess Weight Loss (DEWL) Trial: a randomised controlled trial of high-protein versus high-carbohydrate diets over 2 years in type 2 diabetes.

AIMS/HYPOTHESIS: To compare the effectiveness of low-fat high-protein and low-fat high-carbohydrate dietary advice on weight loss, using group-based interventions, among overweight people with type 2 diabetes. Study design Multicentre parallel (1:1) design, blinded randomised controlled trial. METHODS: Individuals with type 2 diabetes aged 30­75 years and a BMI >27 kg/m2 were randomised, by an independent statistician using sequentially numbered sealed envelopes, to be prescribed either a low-fat high-protein (30% of energy as protein, 40% as carbohydrate, 30% as fat) or a low-fat high carbohydrate(15% of energy as protein, 55%as carbohydrate,30% as fat) diet. Participants attended 18 group sessions over 12 months. Primary outcomes were change in weight and waist circumference assessed at baseline, 6 and 12 months.Secondary outcomes were body fatness, glycaemic control,lipid profile, blood pressure and renal function. A further assessment was undertaken 12 months after the intervention.Research assessors remained blinded to group allocation throughout. Intention-to-treat analysis was performed. RESULTS: A total of 419 participants were enrolled (mean±SDage 58±9.5 years,BMI 36.6±6.5 kg/m2 and HbA1c 8.1±1.2%(65 mmol/mol)). The study was completed by 70%(294/419).No differences between groups were found in change in weight or waist circumference during the intervention phase or the 12-month follow-up. Both groups had lost weight (2­3 kg, p<0.001) and reduced their waist circumference (2­3 cm, p<0.001) by 12 months and largely maintained this weight loss for the following 12 months. By 6 months, the difference in self-reported dietary protein between groups was small (1.1%total energy; p<0.001). No significant differences between groups were found in secondary outcomes: body fatness, HbA1c, lipids, blood pressure and renal function.There were no important adverse effects. CONCLUSIONS/INTERPRETATION: In a 'real-world' setting, prescription of an energy-reduced low-fat diet, with either increased protein or carbohydrate, results in similar modest losses in weight and waist circumference over 2 years

Diabetes outpatient care before and after admission for diabetic foot complications.

OBJECTIVE: To assess the number of patients admitted with a diabetic foot complication to a regional teaching hospital over a 12-month period (July 2005 to June 2006) and determine the percentage that went though an optimal diabetes outpatient management pathway before and after this admission. METHOD: Diabetic inpatients with foot ulcers and infections were identified through the relevant International Classification of Diseases (ICD) codes. Both inpatient and outpatient data were obtained through the local electronic patient management system and review of clinical notes. RESULTS: Forty-nine patients were admitted to hospital with diabetic foot ulcers or infections during the audit period. Median age was 66 years and 67% were male. The most common admitting speciality was vascular surgery. The main associated procedure was toe amputation. In the six month period before and after the index admission, 63% of patients were seen by a health professional at the diabetes centre before or after the admission. 45% of patients were seen at the diabetes centre before and after the admission; 33% were seen by a podiatrist before and after the admission. However, 37% had no contact with the diabetes Centre and 51% did not see a podiatrist from the diabetes centre at any time during the six months before and after their admission. CONCLUSION: Despite the availability of a multidisciplinary high risk foot clinic, only 45% of patients admitted to our regional hospital during the audit period followed an interdisciplinary pathway that included specialist diabetes input of some form and only 33% were assessed by a specialist diabetes podiatrist both before and after their hospital admission. A formalised patient pathway is likely to improve clinical management and may minimise further admissions. In this way it will help reduce morbidity and mortality in this high-risk patient group. In the future, this might best be achieved using an electronic referral and decision support system.

Safety and efficacy of inhaled insulin (AERx iDMS) compared with subcutaneous insulin therapy in patients with Type 1 diabetes: 1-year data from a randomized, parallel group trial.

AIMS: Assessment of the long-term safety and efficacy of liquid inhaled insulin via AERx insulin Diabetes Management System (iDMS) in a basal/bolus treatment regimen of adults with Type 1 diabetes. METHODS: Patients were randomized 2 : 1 to prandial inhaled (n = 205) or subcutaneous (s.c.) (n = 99) insulin, plus one/two daily injections of neutral protamine Hagedorn (NPH) insulin for 12 months. The primary endpoints were pulmonary function tests (PFT) and baseline changes in chest X-rays at 12 months. Safety and efficacy assessments were measured at regular intervals. RESULTS: PFTs after 12 months were comparable between the groups, except for reduced per cent of predicted carbon monoxide lung diffusing capacity with inhaled insulin (difference: -2.03%, P = 0.04) occurring after the first 3 months and then stabilizing. There were no apparent treatment differences in chest X-rays. Overall risk of hypoglycaemia [risk ratio (RR) 1.02, P = 0.83] and adverse events were comparable between groups. Risk of nocturnal hypoglycaemia was higher in the inhaled group (RR 1.58, P = 0.001). Cough [10% (inhaled); 3% (s.c.)] tended to be mild in nature. Inhaled insulin was non-inferior to s.c. insulin for change in glycated haemoglobin (HbA(1c)) after 12 months [difference 0.18% (CI 95%-0.04; 0.39)]. At trial end, mean laboratory measured fasting plasma glucose was lower in the inhaled group (inhaled 9.2 mmol/l; s.c. 11.7 mmol/l; difference: -2.53 mmol/l, P < 0.001). CONCLUSIONS: The safety and efficacy results in this trial were similar to those reported with other inhaled insulins; however, inhaled insulin using AERx iDMS requires further optimization to reduce nocturnal hypoglycaemia before it has comparable safety and efficacy to s.c. insulin aspart.

An alternative method of blood-feeding Culicoides imicola and other haematophagous Culicoides species for vector competence studies.

The use of cotton wool pads saturated with blood/virus mixture for oral infection attempts was compared to membrane feeding for the assessment of vector competence in C. imicola Kieffer and C. bolitinos Meiswinkel (Diptera, Ceratopogonidae). Although lower infection rates were obtained using pad feeding, it was possible to clearly distinguish the levels of competence between species as well as differences in virus infection rates for various serotypes of bluetongue virus. Reduced infection rates with cotton pad feeding was partly due to a smaller volume of blood meals taken up. However, the method described is likely to be useful in situations where membrane feeding is not viable to separate populations with significant differences in vector competence.

Prospective audit of conversion from regular to lispro insulin during routine clinical care.

BACKGROUND: Randomized controlled trials show that lispro insulin has the potential to improve glycaemic control. Observational, practice-based studies provide information that is complementary to that obtained from randomized controlled trials and results of both types of studies are of relevance when advising patients of likely outcomes during routine clinical care. AIMS: This prospective audit aimed to determine whether conversion from regular (short-acting, soluble) preprandial insulin to lispro during routine clinical care improved glycated haemoglobin. METHODS: Eligible patients were those using regular insulin before main meals and a basal neutral protamine Hagedorn (NPH) insulin. Study group patients were those who chose to convert to lispro insulin. Patients who elected not to change their regimen were used as a comparison group. Follow up was for a minimum of 1 year. RESULTS: Glycated haemoglobin (HbA(1c)) and body mass index showed no change in either the study or comparison groups. Post-hoc analysis revealed that the patients most likely to improve their HbA(1c) on lispro were those with a higher baseline HbA(1c). Patients using lispro reported a decreased frequency of hypoglycaemia and improved convenience of use. CONCLUSIONS: Administration of lispro insulin was perceived by patients as convenient to use and was also associated with less hypoglycaemia when compared with the use of regular insulin. There was, however, no improvement in HbA(1c). This finding may be informative when advising patients during routine clinical care of the likely metabolic outcome of changing their insulin regimen.

Testing the effectiveness of techniques for reducing heat strain in Royal Navy nuclear, biological and chemical cleansing stations' teams.

Nine personnel simulating the work of an NBC cleansing station (CS) in conditions expected in Middle Eastern waters had a limited work duration due to incapacitating heat strain. When the subjects were allowed five minutes rest periods after every 10 minutes of work, the endurance of seven of the subjects was limited to between 75-105 minutes due to heat strain and heat illness. By the point of withdrawal mean (SD) rectal temperature (Tre) had risen by 1.8 degrees C (0.4 degree C). The other two subjects were withdrawn earlier because they reached cardiac safety limits. When the hands were immersed (HI) in 10 degrees C water during the five minute rest periods heat strain was significantly lower (P < 0.01) and work endurance times were increased. One subject was withdrawn early on reaching cardiac safety limits, two on reaching Tre limits (39 degrees C) at 105 minutes, and six subjects completed the 180 minute exposure with a final Tre of 38.4 degrees C (0.3 degree C). Using 'iced' (0 degree C) rather than 10 degrees C water for HI further reduced heat strain (P < 0.01) and increased endurance times. Three subjects were withdrawn early on reaching cardiac safety limits, the remaining six completing the 180 minute exposure, with a final Tre of 38.3 degrees C (0.5 degree C). Using an ice-vest (IV) in conjunction with HI further reduced heat strain (P < 0.01) and increased endurance times. Two subjects were withdrawn early on reaching cardiac safety limits, the remaining seven completing the 180 minute exposure, with a final Tre of 38.2 degrees C (0.8 degree C) when 10 degrees C HI water was used, and Tre 38.0 degrees C (0.4 degree C) when 0 degree C HI water was used. There were no reports of finger numbness or loss of dexterity due to HI, and all personnel were able to remove their own individual Protective Equipment (IPE) without difficulty. It is expected that using HI will not reduce the ability to decontaminate or undress others. The HI technique and IV equipment should be introduced into the Fleet. 'Iced' water should be used in preference to 10 degrees C, although any water colder than 25 degrees C will provide some benefit. The IVs increased torso girth and personnel should try them on (with frozen ice packs inserted) prior to their use and ensure that their protective clothing still fits, or obtain a larger size.

Metabolic control and psychological sense of control in women with diabetes mellitus. Alternative considerations of the relationship.

PURPOSE: Identifying psychological strategies to buffer the adverse outcomes in people with diabetes mellitus (DM) remains a priority for many health professionals. While 'locus of control' (LOC) has been repeatedly investigated to this end, research findings are contradictory. The development of more complex appraisals of psychological control, and the utilization of control inventories deriving from such analyses, presents a way forward from such contradictions. METHODS: Employing such a measure, this study examines the relationship between metabolic control and psychological sense of control in 96 women with DM. RESULTS: Optimal metabolic control is significantly associated with overall sense of control, while poor metabolic control was significantly associated with experiences of loss of psychological control and feelings of inadequacy. Furthermore, poor metabolic control was significantly associated with reduced control in the specific domains of interpersonal relationships and bodily functions. CONCLUSIONS: Multidimensional control inventories enable a more complex appraisal of the relationship between metabolic control and psychological control, and in doing so, provide a way forward from problems arising from reliance on LOC constructs. Interventions for DM management relying on aspects of psychological control need to target domains beyond traditional issues of self and bodily functions.

Diabetes in New Zealand.

While the ethnic make up of the New Zealand population is predominantly European, the Polynesian population, consisting of indigenous New Zealand Maori and more recent immigrants from the other Pacific Islands is increasing rapidly. The prevalence of diabetes in these Polynesians is high. There is also an increasing prevalence of obesity, and obesity is a greater problem amongst Polynesian people. The number of elderly people in the population is increasing. All of these demographic changes are increasing the incidence and prevalence of Type 2 diabetes. The incidence of Type 1 diabetes is also rising, although the reasons for this are unknown. Diabetic nephropathy is the most common cause of end stage renal failure in New Zealand. Polynesian people with diabetes, and in particular Maori, have a very high rate of diabetic nephropathy and develop renal failure at a more rapid rate than European patients with nephropathy relating to Type 1 diabetes. The propensity for Maori patients with Type 2 diabetes to develop renal failure may relate to a younger age at the onset of diabetes, a genetic susceptibility to nephropathy, and socio-economic or cultural factors leading to less adequate medical care.

Diabetes complication screening in general practice: a two pass audit with benchmarking.

AIM: To determine whether a two pass audit cycle of diabetes complication screening improves screening rates. METHODS: General practitioners in North Canterbury were invited to participate in a diabetes complications screening audit. Key complication screening tasks and maximum screening intervals were agreed. Patients with diabetes were identified in the primary care setting. General practitioners were given the option of participating in group feedback sessions between the first and second passes of the audit cycle. RESULTS: 106 general practitioners and 2234 patients participated in the first pass. Ninety-three of these 106 general practitioners and 2169 patients participated in the second pass. Screening rates either improved or remained unchanged and a small improvement was seen in the study population's risk factor profile (i.e. total cholesterol and glycated haemoglobin). The group feedback sessions facilitated discussion on interpretation of results from the benchmarking exercise, the optimal time interval between screening procedures and the development of general practice diabetes data sets. CONCLUSION: This two pass primary care audit of diabetes complications screening resulted in improved screening rates for diabetes complications and a small improvement in the study population's risk factor profile.

Elevated glycine betaine excretion in diabetes mellitus patients is associated with proximal tubular dysfunction and hyperglycemia.

In an ambulatory population of diabetic subjects (Type 1 and Type 2), the urine excretion of the renal osmolyte, glycine betaine, was compared to known markers of glycemic control, renal dysfunction and to the excretion of related betaines, including trigonelline, proline betaine, carnitine and acetyl-carnitine. Of the 85 subjects, 20 patients had urine glycine betaine concentrations above the reference range for normal subjects. Plasma glycine betaine concentrations were within reference ranges for normal subjects. Patients with elevated glycine betaine excretion tended to have lower plasma glycine betaine concentrations, but this did not reach statistical significance. One way analysis of variance found excretion is independent of treatment, duration of diagnosed diabetes, blood pressure and body mass index (BMI). An association between glycine betaine excretion and glycemic control was observed with statistically significant correlations occurring with both plasma glucose (r = 0.43, P < 0.001) and glycated haemoglobin (HbA1c) (r = 0.35, P < 0.005). The excretion of carnitine, acetyl-carnitine and proline betaine were related to glycine betaine excretion (r = 0.49, P < 0.001; r = 0.40, P < 0.001; r = 0.27, P < 0.05, respectively). Urine carnitine and acetyl-carnitine concentrations were also related to plasma glucose concentrations (r = 0.30, P < 0.01). Increased urine retinol binding protein concentrations (RBP), a marker of proximal tubular dysfunction, correlated with elevated urine glycine betaine excretion and plasma HbA1c (r = 0.28, P < 0.01). These results suggest poor glycemic control is associated with the increase in urine glycine betaine, carnitine, acetyl-carnitine and RBP excretion in diabetic patients. However, < 50% of the observed increase in glycine betaine excretion has been accounted for by the variables measured, suggesting other unidentified processes may also be involved.

Cerebrovascular disease as a general medicine discharge diagnosis: assessment of diagnostic agreement on case note review.

BACKGROUND: Accurate clerical coding of discharge diagnoses is important partly because results may be used to derive a recommended costing for hospital length of stays (LOS). Some authors think that discharge coding undertaken by clinicians will result in less diagnostic misclassification than clerical coding. This presupposes a high degree of between-observer diagnostic agreement between clinicians. AIMS: To compare discharge coding undertaken by two general physicians, for patients receiving a clerical discharge code of cerebrovascular disease. The recommended LOS was then calculated from each observer's discharge codes using the Physicians Diagnosis Related Group Working Guidebook. RESULTS: Eighty-two cases were coded as stroke by the clerical coder. Both medical coders agreed with this diagnosis in 68 (83%) of these cases. The corresponding figure for cases coded by the clerical coder as transient cerebral ischaemia was 47% (32/68) agreement between all three observers. Correcting for chance agreement between medical observers using the kappa statistic, a value of 0.64 was obtained for the combined stroke and transient cerebral ischaemia discharges, suggesting moderate diagnostic agreement. Using the clerical coder's results, the mean recommended LOS for all cases of cerebrovascular disease over the study period was calculated at 6.68 days. The corresponding values for the two medical coders were 6.68 days and 6.75 days. CONCLUSIONS: Diagnostic agreement between clinicians was moderate. Consideration of alternative diagnostic possibilities and the difficulty in determining the duration of neurological deficit were the main reasons for diagnostic disagreement. The mean recommended LOS was similar, however, when comparing results from all three observers.

A population-based study of bone mineral density in women with longstanding type 1 (insulin dependent) diabetes.

This study aimed to explore multiple determinants of BMD (bone mineral density) in 99 women with long-standing type 1 diabetes, recruited from a population based register of insulin users. BMD was measured using DEXA (dual energy X-ray absorptiometry) at the femoral neck and lumbar spine, age adjusted Z scores were calculated and results compared to those of healthy volunteers. The median age of diabetic subjects was 42 years and the median duration of diabetes was 27 years. BMD was positively associated with body mass index and height at both the lumbar spine and femoral neck. There was a positive association with oral contraceptive pill use and lumbar spine BMD, and peripheral vascular disease was negatively associated with femoral neck BMD. No correlation was seen with either age or duration of diabetes and absolute BMD values. Mean Z score at the femoral neck was -0.12 (95% confidence interval -0.37 to +0.12). At the lumbar spine, the corresponding value was -0.21 (-0.44 to +0.02). Pre- and post-menopausal values for the diabetic subjects and healthy volunteers were found to be similar. In summary, axial BMD values in subjects with long-standing diabetes were similar to those observed in healthy non diabetic populations.