The diabetes management experiences questionnaire: Psychometric validation among adults with type 1 diabetes.

AIMS: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME-Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME-Q captures satisfaction with diabetes management irrespective of treatment modalities. METHODS: The DME-Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre-randomization data (n = 149); responsiveness was examined using baseline and 26-week follow-up data (n = 120). RESULTS: Pre-randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three-factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one-factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales ( α range = 0.74-0.84) and 'Total satisfaction' ( α = 0.85). Convergent validity was demonstrated with moderate correlations between DME-Q 'Total satisfaction' and diabetes distress (PAID: rs = -0.57) and treatment satisfaction (DTSQ; rs = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: rs = -0.16 and - 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy. CONCLUSIONS: The 22-item DME-Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME-Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings.

Initiating or switching to insulin degludec/insulin aspart in a real-world population of adults with type 2 diabetes in Australia: results from a prospective, non-interventional study.

BACKGROUND: Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec and insulin aspart for the treatment of people with diabetes and suboptimal glycaemic control. Few real-world studies of IDegAsp treatment have been conducted. Here, we report results from the Australian cohort of the global ARISE study of real-world IDegAsp use. AIMS: To investigate glycaemic control and other clinical outcomes in people with type 2 diabetes (T2D) treated with IDegAsp in a real-world setting in Australia. METHODS: A total of 183 adults with T2D initiating or switching to IDegAsp in the Australian cohort of the open-label, non-interventional ARISE study were followed for 26-36 weeks from August 2019 to December 2020. RESULTS: IDegAsp was associated with significant reductions from baseline to end of study (EOS) in mean glycated haemoglobin (estimated change -0.8% (95% confidence interval (CI): -1.05 to -0.56; P < 0.0001)), fasting plasma glucose (-1.6 mmol/L (95% CI: -2.49 to -0.63; P = 0.0017)) and body weight (-2.6 kg (95% CI: -3.68 to -1.55; P < 0.0001)). In insulin-experienced patients, the mean total daily insulin dose did not change significantly (estimated change from baseline to EOS 3.8 (95% CI: -3.70 to 11.21; P = 0.3202)). The proportion of patients experiencing hypoglycaemia numerically decreased during the study (non-severe: 14.2-10.9%; nocturnal non-severe: 4.9-2.2%; and severe: 2.2-0%). CONCLUSIONS: Initiating or switching to IDegAsp in a real-world population of people with T2D in Australia was associated with significant improvements in glycaemic control and body weight, and numerically lower levels of hypoglycaemia compared with baseline.

Absolute cardiovascular risk assessment using 'real world' clinic blood pressures compared to standardized unobserved and ambulatory methods: an observational study.

Clinic blood pressure (BP) is recommended for absolute cardiovascular disease (CVD) risk assessment. However, in 'real-world' settings, clinic BP measurement is unstandardised and less reliable compared to more rigorous methods but the impact for absolute CVD risk assessment is unknown. This study aimed to determine the difference in absolute CVD risk assessment using real-world clinic BP compared to standardised BP methods. Participants were patients (n = 226, 59 ± 15 years; 58% female) with hypertension referred to a BP clinic for assessment. 'Real-world' clinic BP was provided by the referring doctor. All participants had unobserved automated office BP (AOBP) and 24-h ambulatory BP monitoring (ABPM) measured at the clinic. Absolute CVD risk was calculated (Framingham) using systolic BP from the referring doctor (clinic BP), AOBP and ABPM, with agreement assessed by Kappa statistic. Clinic systolic BP was 18 mmHg than AOBP and daytime ABPM and 22 mmHg higher than 24-h ABPM (p < 0.001). Subsequently, absolute CVD risk scores using clinic BP were higher compared to AOBP, daytime ABPM and 24-h ABPM (10.4 ± 8.1%, 7.8 ± 6.4%, 7.8 ± 6.3%, and 7.3 ± 6.1%, respectively, P < 0.001). As a result, more participants were classified as high CVD risk using clinic BP (n = 89, 40%) compared with AOBP (n = 44, 20%) daytime ABPM (n = 38, 17%) and 24-h ABPM (n = 38, 17%) (p < 0.001) with weak agreement in risk classification (κ = 0.57[0.45-0.69], κ = 0.52[0.41-0.64] and κ = 0.55[0.43-0.66], respectively). Real-world clinic BP was higher and classified twice as many participants at high CVD risk compared to AOBP or ABPM. Given the challenges to high-quality BP measurement in clinic, more rigorous BP measurement methods are needed for absolute CVD risk assessment.

Driving with Type 1 Diabetes: Real-World Evidence to Support Starting Glucose Level and Frequency of Monitoring During Journeys.

There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median [IQR] age 40 [35, 51] years; 11 men) undertook 475 trips (duration 15 [13, 21] min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%; n = 436). Thirteen drivers recorded at least one trip (total n = 39) starting with glucose <90 mg/dL. Among these, driving glucose was <70 mg/dL in five drivers (38%) during 10 trips (26%). Among five drivers (28%), a ≥ 36 mg/dL drop was observed within 20 min of starting their journey. Journey duration was positively associated with maximum glucose change. These findings support current guidelines to start driving with glucose >90 mg/dL, and to be aware that glucose levels may change significantly within 20 min. A CGM-based, in-vehicle display could provide glucose information and alerts that are compatible with safe driving. Clinical Trial Registration number: ACTRN12617000520336.

Meal-time glycaemia in adults with type 1 diabetes using multiple daily injections vs insulin pump therapy following carbohydrate-counting education and bolus calculator provision.

AIMS: To compare meal-time glycaemia in adults with type 1 diabetes mellitus (T1D) managed with multiple daily injections (MDI) vs. insulin pump therapy (IPT), using self-monitoring blood glucose (SMBG), following diabetes education. METHODS: Adults with T1D received carbohydrate-counting education and a bolus calculator: MDI (Roche Aviva Expert) and IPT (pump bolus calculator). All then wore 3-weeks of masked-CGM (Enlite, Medtronic). Meal-times were assessed by two approaches: 1) Set time-blocks (breakfast 06:00-10:00hrs; lunch 11:00-15:00hrs; dinner 17:00-21:00hrs) and 2) Bolus-calculator carbohydrate entries signalling meal commencement. Post-meal masked-CGM time-in-range (TIR) 3.9-10.0 mmol/L was the primary outcome. RESULTS: MDI(n = 61) and IPT (n = 59) participants were equivalent in age, sex, diabetes duration and HbA1c. Median (IQR) education time provided did not differ (MDI: 1.1 h (0.75, 1.5) vs. IPT: 1.1 h (1.0, 2.0); p = 0.86). Overall, daytime (06:00-24:00hrs), lunch and dinner TIR did not differ for MDI vs. IPT participants but was greater for breakfast with IPT in both analyses with a mean difference of 12.8%, (95 CI 4.8, 20.9); p = 0.002 (time-block analysis). CONCLUSION: After diabetes education, MDI and IPT use were associated with similar day-time glycemia, though IPT users had significantly greater TIR during the breakfast period. With education, meal-time glucose levels are comparable with use of MDI vs. pumps.

Less Nocturnal Hypoglycemia but Equivalent Time in Range Among Adults with Type 1 Diabetes Using Insulin Pumps Versus Multiple Daily Injections.

Background: This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG). Methods: Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16 Results: Adults using MDIs (n = 61) versus pump (n = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA1c at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump (P = 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose <54 mg/dL (<3.0 mmol/L): 1.4% (0.1, 5.1) versus 0.5% (0.0, 2.0), respectively (P = 0.012). They also had more CGM hypoglycemia episodes (121 vs. 54, respectively; incidence rate ratio [95% confidence interval] 2.48 [1.51, 4.06]; P < 0.001). Conclusions: Adults with type 1 diabetes using pumps versus MDIs in conjunction with SMBG experienced less nocturnal hypoglycemia, measured by masked CGM, after equivalent diabetes and dietary education in conjunction with insulin dosage calculator provision to all. However, both groups had equivalent TIR. This observation may reflect advantages afforded by flexibility in basal insulin delivery provided by pumps.

Six Months of Hybrid Closed-Loop Versus Manual Insulin Delivery With Fingerprick Blood Glucose Monitoring in Adults With Type 1 Diabetes: A Randomized, Controlled Trial.

OBJECTIVE: To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with type 1 diabetes). RESEARCH DESIGN AND METHODS: Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR; 70-180 mg/dL) during the final 3 weeks. RESULTS: Participants were randomized to HCL (n = 61) or control (n = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA1c was 7.4% (0.9%) (57 [10] mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% [95% CI 11, 19]; P < 0.0001). For HCL, HbA1c was lower (median [95% CI] difference -0.4% [-0.6, -0.2]; -4 mmol/mol [-7, -2]; P < 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9]; P < 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively. CONCLUSIONS: In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA1c, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous.

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol.

INTRODUCTION: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months' closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes. METHODS AND ANALYSIS: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users. ETHICS AND DISSEMINATION: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12617000520336; Pre-results.

Vascular responses to IGF-I and insulin are impaired in aortae of hypertensive rats.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) and insulin are important vasoactive peptides but little is known about their effects in hypertension. DESIGN: We compared the responses of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rat aortae to IGF-I and insulin. METHODS: Aortae were removed from WKY and SHRSP, cut into 2-3 mm rings, and contractile responses to phenylephrine and endothelin-1 studied in organ chambers in the presence of vehicle, IGF-I (0.1 micromol/l) or insulin (0.1 micromol/l). In addition, the effects of nitric oxide synthase (NOS) inhibition, phosphatidylinositol 3-kinase (PI3-kinase) inhibition and superoxide scavenging on these responses were investigated. RESULTS: Incubation with IGF-I and insulin caused attenuation of phenylephrine-induced and endothelin-1-induced vasoconstriction in arteries from normotensive but not hypertensive animals. In the arteries from WKY rats, co-incubation with either wortmannin or LY294002, inhibitors of PI3-kinase, attenuated the effect of IGF-I. The vasorelaxant effect of IGF-I was also abolished by removal of the endothelium or addition of the NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME). Co-incubation with tiron, a superoxide scavenger, suggested that the attenuation of IGF-I vasodilation in SHRSP arteries was not due to excess superoxide production. CONCLUSION: In WKY, IGF-I/insulin attenuate phenylephrine-mediated constrictions via PI3-kinase/nitric oxide pathways. In contrast, in SHRSP these pathways are dysfunctional and IGF-I has little effect on vascular responses.

Multiple endocrine neoplasia type 1 (MEN 1) is associated with an increased prevalence of diabetes mellitus and impaired fasting glucose.

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant syndrome characterized by primary hyperparathyroidism, pituitary neoplasia and foregut lineage neuroendocrine tumours. It has also been associated with premature cardiovascular death. As diabetes is a risk factor for increased cardiovascular mortality we investigated the prevalence and clinical correlates of glycaemic abnormalities in a large MEN 1 kindred. PATIENTS AND DESIGN: The glycaemic status of 72 MEN 1 affected and 133 unaffected members of a single large MEN 1 pedigree was assessed. Fasting glucose results were categorized and compared using WHO criteria. Associations between glycaemic status and MEN 1 phenotype were assessed. RESULTS: Thirteen (18.1%) patients with MEN 1 compared to 5 (3.8%) control patients were diabetic (P < 0.001). Six (8.3%) MEN 1 patients had impaired fasting glucose compared to 4 (3%) of controls (P < 0.05). Of patients with MEN 1, uncontrolled hypercalcaemia (P < 0.05) and elevated serum gastrin (P < 0.05) were more common amongst patients diagnosed with abnormal glycaemia than those with normoglycaemia. There was a nonsignificant trend for elevated chromogranin A, pancreatic polypeptide, gastric inhibitory polypeptide (but not glucagon) and history of bronchopulmonary carcinoid in MEN 1 patients with elevated glycaemia. CONCLUSIONS: Diabetes and impaired fasting glucose occur significantly more frequently amongst MEN 1 patients than controls and is associated with uncontrolled hyperparathyroidism and evidence of enteropancreatic hyperstimulation.

Growth hormone replacement reduces C-reactive protein and large-artery stiffness but does not alter endothelial function in patients with adult growth hormone deficiency.

Hypopituitary patients have an increased risk of vascular mortality that may relate to growth hormone deficiency (GHD). We investigated the effects of 6 months of GH therapy on large- and small-artery function and high-sensitivity C-reactive protein (hsCRP) in a cohort of GH-deficient patients. Sixteen hypopituitary patients were randomized to 6 months of GH therapy or no treatment, then vice versa. hsCRP, 24-h blood pressure (BP) and pulse wave velocity (PWV) were measured and resistance arteries were used to construct concentration-response curves to endothelium-dependent and -independent agents. GH therapy increased IGF-1 from 60 +/- 7.2 to 167 +/- 16.2 microg/l [confidence interval (CI) 94.9, 138.8, P < 0.001]. hsCRP declined after 6 months of GH from 3.8 +/- 0.88 to 2.0 +/- 0.49 mg/l (CI 0.73, 3.57, P = 0.006). Mean arterial BP fell from 91.7 +/- 1.5 to 89.3 +/- 1.2 mmHg (CI 0.81, 4.07, P = 0.005), as did PWV (8.1 +/- 0.4 to 6.7 +/- 0.5 m/s). The decline in PWV correlated with the decline in hsCRP (r = 0.68, P = 0.01). Resistance artery function was unchanged after GH therapy. GH replacement may lead to differentially altered production of vasorelaxant agents from the endothelium of large and small arteries. Reduction in vascular inflammation may be associated with reduced vascular risk.

Growth hormone deficiency and vascular risk.

The importance of growth hormone deficiency (GHD) in adult life has become more apparent over the last decade. As well as a distinct clinical syndrome there is a significant excess risk of cardiovascular disease. Although it is difficult to ascertain what part is played by the original pituitary disorder and the concomitant replacement hormonal therapies, there is clear evidence that GHD is associated with known cardiovascular risk factors such as body shape, lipid profile, insulin resistance, blood pressure, vessel wall morphology and haemostatic factors. Novel means of assessing vascular risk such as pulse wave velocity and flow-mediated dilatation can also estimate the risk without invasive procedures. The role of possible mediators of endothelial function such as nitric oxide and free radicals is being investigated further. Replacement of GH in GH-deficient patients leads to many effects on the above indices, some but not all of which are associated with reduced vascular risk. Long-term follow-up studies of morbidity and mortality are required for an accurate assessment of the beneficial effects of therapy.