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.

Euglycemic Ketoacidosis in Two Patients Without Diabetes After Introduction of Sodium-Glucose Cotransporter 2 Inhibitor for Heart Failure With Reduced Ejection Fraction.

OBJECTIVE: Ketoacidosis induced by sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment has been consistently observed in clinical practice in patients with type 2 diabetes despite minimal indication from the landmark cardiovascular outcome trials. It has been postulated that individuals without diabetes will not develop this complication due to an adequate insulin secretory capacity, which will protect against significant ketone formation. Cardiovascular outcome trials examining SGLT2i use in individuals with heart failure but not diabetes have not reported ketoacidosis. RESEARCH DESIGN AND METHODS: We describe the first two case reports of severe nondiabetic ketoacidosis after initiation of an SGLT2i for the treatment of heart failure with reduced ejection fraction, and we describe the management strategies employed and implication for the pathophysiology of SGLT2i-associated ketoacidosis. RESULTS: Each individual presented with ketoacidosis triggered by reduced oral nutrition intake. For both individuals, ketoacidosis resolved with intravenous glucose administration, encouragement of consumption of oral glucose-containing fluid, and minimal insulin administration. CONCLUSIONS: These two cases demonstrate that SGLT2i-associated ketoacidosis is possible in individuals without diabetes.

Universal Subsidized Continuous Glucose Monitoring Funding for Young People With Type 1 Diabetes: Uptake and Outcomes Over 2 Years, a Population-Based Study.

OBJECTIVE: Continuous glucose monitoring (CGM) is increasingly used in type 1 diabetes management; however, funding models vary. This study determined the uptake rate and glycemic outcomes following a change in national health policy to introduce universal subsidized CGM funding for people with type 1 diabetes aged <21 years. RESEARCH DESIGN AND METHODS: Longitudinal data from 12 months before the subsidy until 24 months after were analyzed. Measures and outcomes included age, diabetes duration, HbA1c, episodes of diabetic ketoacidosis and severe hypoglycemia, insulin regimen, CGM uptake, and percentage CGM use. Two data sources were used: the Australasian Diabetes Database Network (ADDN) registry (a prospective diabetes database) and the National Diabetes Service Scheme (NDSS) registry that includes almost all individuals with type 1 diabetes nationally. RESULTS: CGM uptake increased from 5% presubsidy to 79% after 2 years. After CGM introduction, the odds ratio (OR) of achieving the HbA1c target of <7.0% improved at 12 months (OR 2.5, P < 0.001) and was maintained at 24 months (OR 2.3, P < 0.001). The OR for suboptimal glycemic control (HbA1c ≥9.0%) decreased to 0.34 (P < 0.001) at 24 months. Of CGM users, 65% used CGM >75% of time, and had a lower HbA1c at 24 months compared with those with usage <25% (7.8 ± 1.3% vs. 8.6 ± 1.8%, respectively, P < 0.001). Diabetic ketoacidosis was also reduced in this group (incidence rate ratio 0.49, 95% CI 0.33-0.74, P < 0.001). CONCLUSIONS: Following the national subsidy, CGM use was high and associated with sustained improvement in glycemic control. This information will inform economic analyses and future policy and serve as a model of evaluation diabetes technologies.

Acute pleiotropic effects of dapagliflozin in type 2 diabetic patients with heart failure with reduced ejection fraction: a crossover trial.

AIMS: This study aimed to explore the rapid effects of dapagliflozin in heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We studied the functional, echocardiographic, electrophysiological, lung ultrasound, ambulatory blood pressure (BP), microvascular and macrovascular function, and biochemical effects of 2 week treatment with dapagliflozin in 19 type 2 diabetic HFrEF patients in a double-blind, crossover, placebo-controlled trial. Dapagliflozin had no significant effect on clinical, functional, or quality of life parameters. Dapagliflozin reduced systolic BP [114 (105, 131) vs. 106 (98, 113) mmHg, P < 0.01] and diastolic BP [71 (61, 78) vs. 62 (55, 70) mmHg, P < 0.01]. There was no effect on cardiac chamber size, ventricular systolic function, lung ultrasound, or arterial wave reflection. Dapagliflozin increased creatinine [117 (92, 129) vs. 122 (107, 135) µmol/L, P < 0.05] and haemoglobin [135 (118, 138) vs. 136 (123, 144) g/L, P < 0.05]. There was a reduction in ventricular ectopy [1.4 (0.1, 2.9) vs. 0.2 (0.1, 1.4) %, P < 0.05] and an increase in standard deviation of normal heart beat intervals [70 (58, 90) vs. 74 (62, 103), P < 0.05]. Unexpectedly, dapagliflozin increased high-sensitivity troponin T [25 (19, 37) vs. 28 (20, 42) ng/L, P < 0.01] and reduced reactive hyperaemia index [1.29 (1.21, 1.56) vs. 1.40 (1.23, 1.84), P < 0.05]. CONCLUSIONS: After 2 weeks, while multiple parameters supported BP reduction and haemoconcentration with dapagliflozin, reduction in cardiac filling pressure, lung water, and functional improvement was not shown. Reduced ventricular ectopic burden suggests an early antiarrhythmic benefit. The small increase in troponin T and the reduction in the reactive hyperaemia index warrant further mechanistic exploration in this treatment of proven mortality benefit in HFrEF.

Involvement of the MEN1 gene locus in familial isolated hyperparathyroidism.

BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is a hereditary disorder characterised by uni- or multiglandular parathyroid disease. A subset of families are likely to be genetic variants of other familial tumour syndromes in which PHPT is the main feature, for example multiple endocrine neoplasia type 1 (MEN 1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT). OBJECTIVE: To investigate seven families diagnosed with FIHP, each with two to eight affected family members, to clarify the underlying genetic mechanism. METHODS: The entire MEN1 gene was sequenced for germline mutations and, in addition, tumour specimens were analysed in comparative genomic hybridisation and loss of heterozygosity studies. RESULTS: Two families exhibited MEN1 mutations, L112V and 1658delG, which were associated with loss of the wild-type 11q13 alleles in all tumours analysed. In the remaining five families, no MEN1 mutation was identified. CONCLUSION: These results support the involvement of the MEN1 tumour suppressor gene in the pathogenesis of some of the FIHP kindreds. However, loss on chromosome 11 was seen in all tumours exhibiting somatic deletions, although in two families the tumour deletions involved 11q distal to MEN1. We conclude that the altered MEN1 gene function is of importance in the development of FIHP.