Peter Mansell

Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the U.K. DAFNE experience.

OBJECTIVE DAFNE (Dose Adjustment For Normal Eating), a structured education program in flexible insulin therapy, has been widely adopted in the U.K. after validation in a randomized trial. To determine benefits in routine practice, we collected biomedical and psychological data from all participants attending during a 12-month period. RESEARCH DESIGN AND METHODS HbA1c, weight, self-reported hypoglycemia awareness, severe hypoglycemia frequency, PAID (Problem Areas In Diabetes), HADS (Hospital Anxiety and Depression Scale), and EuroQol Group 5-Dimension Self-Report Questionnaire scores were recorded prior to DAFNE and after 1 year. RESULTS Complete baseline and follow-up HbA1c data were available for 639 (54.9%) of 1,163 attendees. HbA1c fell from 8.51 ± 1.41 (mean ± SD) to 8.24 ± 1.29% (difference 0.27 [95% CI 0.16–0.38]; P < 0.001), with a greater mean fall of 0.44% from baseline HbA1c >8.5%. Severe hypoglycemia rate fell from 1.7 ± 8.5 to 0.6 ± 3.7 episodes per person per year (1.1 [0.7–1.4]) and hypoglycemia recognition improved in 43% of those reporting unawareness. Baseline psychological distress was evident, with a PAID score of 25.2 and HADS scores of 5.3 (anxiety) and 4.8 (depression), falling to 16.7 (8.5 [6.6–10.4]), 4.6 (0.7 [0.4–1.0]), and 4.2 (0.6 [0.3–0.8]), respectively (all P < 0.001 at 1 year). Clinically relevant anxiety and depression (HADS ≥8) fell from 24.4 to 18.0% and 20.9 to 15.5%, respectively. CONCLUSIONS A structured education program delivered in routine clinical practice not only improves HbA1c while reducing severe hypoglycemia rate and restoring hypoglycemia awareness but also reduces psychological distress and improves perceived well-being.

Substantial reductions in the number of diabetic ketoacidosis and severe hypoglycaemia episodes requiring emergency treatment lead to reduced costs after structured education in adults with Type 1 diabetes.

To determine the impact of structured education promoting flexible intensive insulin therapy on rates of diabetic ketoacidosis, and the costs associated with emergency treatment for severe hypoglycaemia and ketoacidosis in adults with Type 1 diabetes.

Investigation of the haemodynamic effects of exenatide in healthy male subjects

AIMS In clinical studies of glucagon-like peptide-1 (GLP-1) agonists used in the management of patients with type 2 diabetes, there is often a small accompanying fall in blood pressure. The mechanism underlying this effect is not known, although exenatide, a GLP-1 mimetic, has acute regional vasodilator properties in rats. We have therefore studied the haemodynamic effects of exenatide in healthy male volunteers. METHODS We compared the effects of a single 10 µg subcutaneous injection of exenatide with placebo in a double-blind, randomized, crossover study. For 2 h after dosing, haemodynamic measurements were made using a Finometer, venous occlusion plethysmography and Doppler ultrasound. The urine sodium : creatinine excretion ratio was determined. RESULTS At the end of the study when exenatide was compared with placebo, heart rate had risen by a mean of 8.2 (95% CI 4.2, 12.2, P < 0.01) beats min(-1) , cardiac output by a mean of 1.2 (95% CI 0.42, 20.3, P < 0.05) l min(-1) and total peripheral resistance had fallen by 120 (95% CI -8, -233, P < 0.05) dyn s cm(-5) .There were no differences in blood pressure. The urinary sodium : creatinine ratio was increased by mean 12.4 (95% CI 4.6, 20.2, P < 0.05) mmol mmol(-1) when exenatide was compared with placebo. CONCLUSIONS Exenatide has significant haemodynamic effects in healthy volunteers. The results of this study are consistent with exenatide having both vasodilator and natriuretic properties. The vascular changes may contribute to the hypotensive effect of exenatide when used chronically in patients with diabetes.

Glycaemic control and weight 7 years after Dose Adjustment For Normal Eating (DAFNE) structured education in Type 1 diabetes

Diabet. Med. 29, 807–812 (2012)

Measurement of fetal fat in utero in normal and diabetic pregnancies using magnetic resonance imaging

To assess the reliability of magnetic resonance imaging (MRI) to measure fetal fat volume in utero, and to study fetal growth in women with and without diabetes in view of the increased prevalence of macrosomia in the former.

Variability in fasting lipid and glycogen contents in hepatic and skeletal muscle tissue in subjects with and without type 2 diabetes: a 1H and 13C MRS study.

The measurement of tissue lipid and glycogen contents and the establishment of normal levels of variability are important when assessing changes caused by pathology or treatment. We measured hepatic and skeletal muscle lipid and glycogen levels using 1H and 13C MRS at 3 T in groups of subjects with and without type 2 diabetes. Within‐visit reproducibility, due to repositioning and instrument errors was determined from repeat measurements made over 1 h. Natural variability was assessed from separate measurements made on three occasions over 1 month. Hepatic lipid content was greater in subjects with diabetes relative to healthy subjects (p = 0.03), whereas levels of hepatic and skeletal muscle glycogen, and of intra‐ and extra‐myocellular lipid, were similar. The single‐session reproducibility values (coefficient of variation, CV) for hepatic lipid content were 12% and 7% in groups of subjects with and without diabetes, respectively. The variability of hepatic lipid content over 1 month was greater than the reproducibility, with CV = 22% (p = 0.08) and CV = 44% (p = 0.004) in subjects with and without diabetes, respectively. Similarly, levels of variation in basal hepatic glycogen concentrations (subjects with diabetes, CV = 38%; healthy volunteers, CV = 35%) were significantly larger than single‐session reproducibility values (CV = 17%, p = 0.02 and CV = 13%, p = 0.05, respectively), indicating substantial biological changes in basal concentrations over 1 month. There was a decreasing correlation in measurements of both hepatic lipid and glycogen content with increasing time between scans. Levels of variability in intra‐ and extra‐myocellular lipid in the soleus muscle, and glycogen concentrations in the gastrocnemius muscle, tended to be larger than expected from single‐session reproducibility, although these did not reach significance. Copyright

Linguistic and Psychometric Validation of the Diabetes-Specific Quality-of-Life Scale in U.K. English for Adults With Type 1 Diabetes

OBJECTIVE To develop a linguistically and psychometrically validated U.K. English (U.K./Ireland) version of the Diabetes-Specific Quality-of-Life Scale (DSQOLS) for adults with type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted independent forward and backward translation of the validated German DSQOLS. An iterative interview study with health professionals (n = 3) and adults with type 1 diabetes (n = 8) established linguistic validity. The DSQOLS was included in three Dose Adjustment for Normal Eating (DAFNE) studies (total N = 1,071). Exploratory factor analysis (EFA) was undertaken to examine questionnaire structure. Concurrent and discriminant validity, internal consistency, and reliability were assessed. RESULTS EFA indicated a six-factor structure for the DSQOLS (social aspects, fear of hypoglycemia, dietary restrictions, physical complaints, anxiety about the future, and daily hassles). High internal consistency reliability was found for these factors and the weighted treatment satisfaction scale (α = 0.85–0.94). All subscales were moderately, positively correlated with the Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) measure, demonstrating evidence of concurrent validity. Lower DSQOLS subscale scores [indicating impaired quality of life (QoL)] were associated with the presence of diabetes-related complications. CONCLUSIONS The DSQOLS captures the impact of detailed aspects of modern type 1 diabetes management (e.g., carbohydrate counting and flexible insulin dose adjustment) that are now routine in many parts of the U.K. and Ireland. The U.K. English version of the DSQOLS offers a valuable tool for assessing the impact of treatment approaches on QoL in adults with type 1 diabetes.

Differences in post-mortem findings after stillbirth in women with and without diabetes.

The reason for the fivefold increased risk of stillbirth in women with diabetes is not known. Further understanding of the underlying mechanisms may facilitate identification of pregnancies at increased risk. We have compared post‐mortem reports in matched pairs of stillbirths in women with and without diabetes.

Fish oil omega-3 fatty acids partially prevent lipid-induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation

Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic-hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater following n6PUFA compared with Control and n3PUFA, suggesting that mitochondrial lipid overload was responsible for the lower insulin action observed. Despite these favourable metabolic effects of n3PUFA, accumulation of total muscle acylcarnitine was not attenuated when compared with n6PUFA. These findings demonstrate that n3PUFA exert beneficial effects on insulin-stimulated skeletal muscle glucose storage and oxidation independently of total acylcarnitine accumulation, which does not always reflect mitochondrial lipid overload.

Maturity onset-type diabetes of the young (MODY): one condition or many?

In 1973 during a study of 92 patients with Type 1 diabetes for 40 years or more, one of us’ found three who did not fit the expected pattern. All were women who had been diagnosed in adolescence and then treated with insulin for over 20 years. None had any microvascular complications, and after 40 years of diabetes all were well controlled on m a l l doses of sulphonylureas. Each woman had a strong family history of a phenotypically similar form of diabetes. Thus of 20 living relatives with a mean duration of diabetes of 22 (range 2-54) years only one was still on insulin, only two had any retinopathy, and none had proteinuria. The pedigrees strongly suggested autosomal dominant inheritance (Figure l ) , and in two of the three families diabetes was associated with a low renal threshold for glucose. A similar form of diabetes had apparently been recognized in the pre-insulin era when the contrast with the dismal prognosis of what was later called Type 1 diabetes must have been very striking. In 191 6 Reisman2 recorded four cases of mild diabetes in children, noted the familial tendency and referred to similar cases in the German literature in which the disease had been named ’diabetes innocens im jugenlichen alter‘. In 1921 at the Royal Society of Medicine, Graham3 presented two unrelated girls with diabetes diagnosed at ages 9 and 1 1 years who had been controlled for at least 5 years on diet alone. Joslin‘s 1924 textbook4 has a table of four patients, each with a strong family history of diabetes, who were diagnosed under age 20 years and survived on diet alone for between 9 and 21 years, leading Joslin to comment that, ‘I always look upon a strong family history as a favourable omen’. The most remarkable was a woman who developed diabetes in 1909 aged 20 years, had a baby in 1916, and was still well in 1923 when Joslin suggested that ‘she should have insulin as a safeguard against complications’. Dominant inheritance