Acceptability and experiences of real-time continuous glucose monitoring in adults with type 2 diabetes using insulin: a qualitative study.

Aims: To explore the lived experiences of initiating real-time continuous glucose monitoring (rt-CGM) use in individuals with type 2 diabetes using insulin. Methods: Twelve semi-structured interviews were conducted amongst individuals with type 2 diabetes taking insulin who were enrolled in the 2GO-CGM randomised controlled trial and had completed 3 months of rtCGM. Interviews were transcribed verbatim and analysed to identify common themes regarding their experiences. Results: The interviews revealed three key themes: i) rtCGM as a facilitator of improved health behaviours; ii) the acceptability of rtCGM systems compared to capillary blood glucose testing; and iii) barriers to the continual usage of rtCGM technology - including: connection difficulties, longevity of the sensors, and local cutaneous reactions to the sensor adhesive. Conclusion: Adults on insulin with type 2 diabetes find rtCGM systems widely acceptable, and easier to engage with than traditional self-monitoring of capillary blood glucose. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01403-9.

Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial.

Purpose: Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group. Methods: A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7-25 years with T1D, a current HbA1c ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes. Conclusion: This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452). Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01397-4.

Real time continuous glucose monitoring in high-risk people with insulin-requiring type 2 diabetes: A randomised controlled trial.

AIMS: To investigate the impact of real-time continuous glucose monitoring (rtCGM) on glycaemia in a predominantly indigenous (Maori) population of adults with insulin-requiring type 2 diabetes (T2D) in New Zealand. METHODS: Twelve-week, multicentre randomised controlled trial (RCT) of adults with T2D using ≥0.2 units/kg/day of insulin and elevated glycated haemoglobin (HbA1c) ≥64 mmol/mol (8.0%). Following a 2-week blinded CGM run-in phase, participants were randomised to rtCGM or control (self-monitoring blood glucose [SMBG]). The primary outcome was time in the target glucose range (3.9-10 mmol/L; TIR) during weeks 10-12, with data collected by blinded rtCGM in the control group. RESULTS: Sixty-seven participants entered the RCT phase (54% Maori, 57% female), median age 53 (range 16-70 years), HbA1c 85 (IQR 74, 94) mmol/mol (9.9 [IQR 8.9, 10.8]%), body mass index (36.7 ± 7.7 kg/m2). Mean (±SD) TIR increased from 37 (24)% to 53 (24)% [Δ 13%; 95% CI 4.2 to 22; P = 0.007] in the rtCGM group but did not change in the SMBG group [45 (21)% to 45 (25)%, Δ 2.5%, 95% CI -6.1 to 11, P = 0.84]. Baseline-adjusted between-group difference in TIR was 10.4% [95% CI -0.9 to 21.7; P = 0.070]. Mean HbA1c (±SD) decreased in both groups from 85 (18) mmol/mol (10.0 [1.7]%) to 64 (16) mmol/mol (8.0 [1.4]%) in the rtCGM arm and from 81 (12) mmol/mol (9.6 [1.1]%) to 65 (13) mmol/mol (8.1 [1.2]%) in the SMBG arm (P < 0.001 for both). There were no severe hypoglycaemic or ketoacidosis events in either group. CONCLUSIONS: Real-time CGM use in a supportive treat-to-target model of care likely improves glycaemia in a population with insulin-treated T2D and elevated HbA1c.

Do-it-yourself continuous glucose monitoring in people aged 16 to 69 years with type 1 diabetes: A qualitative study.

AIMS: In many countries, real-time continuous glucose monitoring (rt-CGM) is not funded, and cost presents a barrier to access. A do-it-yourself conversion of intermittently scanned CGM (DIY-CGM) is a cheaper alternative. This qualitative study aimed to explore user experiences with DIY-CGM in people aged 16 to 69 years with type 1 diabetes (T1D). METHODS: Convenience sampling was used to recruit participants for semi-structured virtual interviews exploring experiences of DIY-CGM use. Participants were recruited after completing the intervention arm of a crossover randomised controlled trial that evaluated DIY-CGM versus intermittently scanned CGM (isCGM). Participants were previously naive to DIY-CGM and rt-CGM but not isCGM. The DIY-CGM intervention consisted of a Bluetooth bridge connected to isCGM, adding rt-CGM functionality over 8 weeks. Interviews were transcribed, then thematic analysis was performed. RESULTS: Interviews were with 12 people aged 16 to 65 years, with T1D: mean age ± SD 43 ± 14 years; baseline mean HbA1c ± SD 60 mmol/mol ± 9.9 (7.6 ± 0.9%) and time in range 59.8% ± 14.8%. Participants perceived that using DIY-CGM improved both glycaemic control and aspects of quality of life. Alarm and trend functionality allowed participants to perceive reduced glycaemic variability overnight and following meals. The addition of a smartwatch increased discrete access to glucose information. There was a high degree of trust in DIY-CGM. Challenges while using DIY-CGM included signal loss during vigorous exercise, alarm fatigue and short battery life. CONCLUSIONS: This study suggests that for users, DIY-CGM appears to be an acceptable alternative method of rt-CGM.

Study protocol: glycaemic outcomes in people with type 2 diabetes initiating continuous glucose monitoring: the 2GO-CGM study.

Purpose: Improving glycaemic control in type 2 diabetes (T2D) is essential to reducing social and health-economic burden of diabetes-related complications. Continuous glucose monitoring (CGM) has been established as beneficial in improving glycaemic control and reducing hypoglycaemia in people with type 1 diabetes, however data in T2D is limited. This study has been designed to assess the effect of initiating real-time CGM (rtCGM) on glycaemic control in a high-risk population of adults with T2D. Secondary objectives are to assess the cost-effectiveness and safety of rtCGM, and the effects of rtCGM on diet/lifestyle and the burden of diabetic complications, including cardiovascular risk. Methods: This multicentre randomised controlled trial (RCT) will be conducted at three sites in New Zealand (Waikato, Christchurch and Dunedin). Eighty adults with T2D on insulin with suboptimal glycaemic control (HbA1c > 8.0% or 64 mmol/mol) will be randomised 1:1 to rtCGM or routine care with self-monitoring of blood glucose levels (SMBG) for three months. This intervention phase will be followed by a three-month continuation phase where SMBG group crossover to use rtCGM. Participants will then be invited to join the extension phase with continued use of rtCGM for a further 12 months. During the extension phase, both groups will independently titrate their insulin under the remote supervision of prescribing diabetes nurse specialists following an insulin titration algorithm. The primary outcome of the study is time in target glucose range (3.9-10 mmol/L or 70-180 mg/dL; TIR). Secondary outcomes include CGM metrics as per consensus statement recommendations, and HbA1c. Additional planned analyses include cardiovascular risk profile, incremental cost-effectiveness analyses, dietary patterns, and qualitative analyses. Trial registration number: The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000889853) on 8 July 2021 and the World Health Organisation International Clinical Trial Registry Platform (Universal Trial Number U1111-1264-5822).

Epidemiology of Diabetic Ketoacidosis in the Waikato Region of New Zealand: 2000-2019.

Aims: Diabetic ketoacidosis (DKA) is not well characterised in New Zealand. This study is aimed at characterising the change in epidemiology and severity of DKA from 2000 to 2019 at a tertiary hospital in the Waikato region of New Zealand. Methods: A retrospective clinical data review of all patients admitted to Waikato District Health Board hospitals with DKA was undertaken. Characteristics and severity of DKA were assessed by type of DKA admission (diagnosed at admission, nonrecurrent, and recurrent), ethnicity, social deprivation, intensive care unit (ICU) admission, and length of hospital stay, with linear regression reporting on changes over time. Results: There were 1254 admissions for DKA (564 individual patients), two-thirds being recurrent events. Nonrecurrent DKA patients were younger, whilst recurrent admissions for DKA were associated with T1D, female gender, greater socioeconomic deprivation, and rural living (all P values < 0.01). DKA admission increased 8-fold between 2000 and 2019, mostly due to an increased number of recurrent events, particularly in Maori and female patients (P < 0.001). ICU admissions increased over time (P < 0.001) whilst length of hospital stay trended down (P = 0.031). Conclusions: The rise in recurrent DKA is concerning, particularly in youth and indigenous Maori. Healthcare inequities need to be addressed, including adequate access to mental health support to ensure optimal outcomes for all patients with diabetes.

Extended Use of an Open-Source Automated Insulin Delivery System in Children and Adults with Type 1 Diabetes: The 24-Week Continuation Phase Following the CREATE Randomized Controlled Trial.

Aim: To assess long-term efficacy and safety of open-source automated insulin delivery (AID) in children and adults (7-70 years) with type 1 diabetes. Methods: Both arms of a 24-week randomized controlled trial comparing open-source AID (OpenAPS algorithm within a modified version of AndroidAPS, preproduction DANA-i™ insulin pump, Dexcom G6 continuous glucose monitor) with sensor-augmented pump therapy (SAPT), entered a 24-week continuation phase where the SAPT arm (termed SAPT-AID) crossed over to join the open-source AID arm (termed AID-AID). Most participants (69/94) used a preproduction YpsoPump® insulin pump during the continuation phase. Analyses incorporated all 52 weeks of data, and combined between-group and within-subject differences to calculate an overall "treatment effect" of AID versus SAPT. Results: Mean time in range (TIR; 3.9-10 mmol/L [70-180 mg/dL]) was 12.2% higher with AID than SAPT (95% confidence interval [CI] 10.4 to 14.1; P < 0.001). TIR was 56.9% (95% CI 54.2 to 59.6) with SAPT and 69.1% (95% CI 67.1 to 71.1) with AID. The treatment effect did not differ by age (P = 0.39) or insulin pump type (P = 0.37). HbA1c was 5.1 mmol/mol lower [0.5%] with AID (95% CI -6.6 to -3.6; P < 0.001). There were no episodes of diabetic ketoacidosis or severe hypoglycemia with either treatment over the 48 weeks. Six participants (all in SAPT-AID) withdrew: three with hardware issues, two preferred SAPT, and one with infusion-site skin irritation. Conclusion: Further evaluation of the community derived automated insulin delivery (CREATE) trial to 48 weeks confirms that open-source AID is efficacious and safe with different insulin pumps, and demonstrates sustained glycemic improvements without additional safety concerns.

Inequity in access to continuous glucose monitoring and health outcomes in paediatric diabetes, a case for national continuous glucose monitoring funding: A cross-sectional population study of children with type 1 diabetes in New Zealand.

Background: Continuous glucose monitoring (CGM) improves glycaemia for people affected by type 1 diabetes (T1D), but is not funded in Aotearoa/New Zealand. This study explores the impact of non-funded CGM on equity of access and associated glycaemic outcomes. Methods: Cross-sectional population-based study collected socio-demographic (age, gender, prioritised ethnicity, socioeconomic status) and clinical data from all regional diabetes centres in New Zealand with children <15 years with T1D as of 1st October 2021. De-identified data were obtained from existing databases or chart review. Outcomes compared socio-demographic characteristics between those using all forms of CGM and self-monitoring of blood glucose (SMBG), and association with HbA1c. Findings: 1209 eligible children were evaluated: 70.2% European, 18.1% Maori, 7.1% Pacific, 4.6% Asian, with even distribution across socioeconomic quintiles. Median HbA1c was 64 mmol/mol (8.0%), 40.2% utilised intermittently scanned (is)CGM, and 27.2% real-time (rt)CGM. CGM utilisation was lowest with Pacific ethnicity (38% lower than Maori) and the most deprived socioeconomic quintiles (quintile 5 vs. 1 adjusted RR 0.69; 95% CI, 0.57 to 0.84). CGM use was associated with regional diabetes centre (P < 0.001). The impact of CGM use on HbA1c differed by ethnicity: Maori children had the greatest difference in HbA1c between SMBG and rtCGM (adjusted difference -15.3 mmol/mol; 95% CI, -21.5 to -9.1), with less pronounced differences seen with other ethnicities. Interpretation: Inequities in CGM use exist based on prioritised ethnicity and socioeconomic status. Importantly, CGM was independently associated with lower HbA1c, suggesting that lack of CGM funding contributes to health disparity in children with T1D. Funding: Australasian Paediatric Endocrine Group (APEG), Canterbury Medical Research Foundation, Starship Foundation.

Open-Source Automated Insulin Delivery in Type 1 Diabetes.

BACKGROUND: Open-source automated insulin delivery (AID) systems are used by many patients with type 1 diabetes. Data are needed on the efficacy and safety of an open-source AID system. METHODS: In this multicenter, open-label, randomized, controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio to use an open-source AID system or a sensor-augmented insulin pump (control). The patients included both children (defined as 7 to 15 years of age) and adults (defined as 16 to 70 years of age). The AID system was a modified version of AndroidAPS 2.8 (with a standard OpenAPS 0.7.0 algorithm) paired with a preproduction DANA-i insulin pump and Dexcom G6 CGM, which has an Android smartphone application as the user interface. The primary outcome was the percentage of time in the target glucose range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) between days 155 and 168 (the final 2 weeks of the trial). RESULTS: A total of 97 patients (48 children and 49 adults) underwent randomization (44 to open-source AID and 53 to the control group). At 24 weeks, the mean (±SD) time in the target range increased from 61.2±12.3% to 71.2±12.1% in the AID group and decreased from 57.7±14.3% to 54.5±16.0% in the control group (adjusted difference, 14 percentage points; 95% confidence interval, 9.2 to 18.8; P<0.001), with no treatment effect according to age (P = 0.56). Patients in the AID group spent 3 hours 21 minutes more in the target range per day than those in the control group. No severe hypoglycemia or diabetic ketoacidosis occurred in either group. Two patients in the AID group withdrew from the trial owing to connectivity issues. CONCLUSIONS: In children and adults with type 1 diabetes, the use of an open-source AID system resulted in a significantly higher percentage of time in the target glucose range than the use of a sensor-augmented insulin pump at 24 weeks. (Supported by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12620000034932.).

The minor allele of the CREBRF rs373863828 p.R457Q coding variant is associated with reduced levels of myostatin in males: Implications for body composition.

OBJECTIVE: The minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples of the Pacific islands (including New Zealand Maori and peoples of Polynesia), with a frequency of up to 25% in these populations. This allele associates with a large increase in body mass index (BMI) but with significantly lower risk of type-2 diabetes (T2D). It remains unclear whether the increased BMI is driven by increased adiposity or by increased lean mass. METHODS: We undertook body composition analysis using DXA in 189 young men of Maori and Pacific descent living in Aotearoa New Zealand. Further investigation was carried out in two orthologous Arg458Gln knockin mouse models on FVB/NJ and C57BL/6j backgrounds. RESULTS: The rs373863828 A allele was associated with lower fat mass when adjusted for BMI (p < 0.05) and was associated with significantly lower circulating levels of the muscle inhibitory hormone myostatin (p < 0.05). Supporting the human data, significant reductions in adipose tissue mass were observed in the knockin mice. This was more significant in older mice in both backgrounds and appeared to be the result of reduced age-associated increases in fat mass. The older male knockin mice on C57BL/6j background also had increased grip strength (p < 0.01) and lower levels of myostatin (p < 0.05). CONCLUSION: Overall, these results prove that the rs373863828 A-allele is associated with a reduction of myostatin levels which likely contribute to an age-dependent lowering of fat mass, at least in males.

The psychological profile of youth and young adults with type 1 diabetes in New Zealand.

BACKGROUND: The psychological status of New Zealanders living with type 1 diabetes (T1D) is unknown. This study's purpose is to determine the prevalence of general wellbeing, diabetes-specific distress, and disordered eating, and explore their relationships with glycemic control. METHODS: Participants were patients aged 15-24 years with T1D (N = 200) who attended their routine multidisciplinary clinic at the Waikato Regional Diabetes Service. They completed questionnaires including the World Health Organization Well-Being Index, the Problem Areas in Diabetes scales, and the Diabetes Eating Problem Survey-Revised. Clinical and demographic information were also collected. RESULTS: Median age of participants was 19.3 years and 14% identified as Maori (indigenous people of Aotearoa New Zealand). Median HbA1c was 73 mmol/mol. One fifth of participants experienced low emotional wellbeing, including 7.5% who experienced likely depression. Diabetes distress was found in 24.1%, and 30.7% experienced disordered eating behaviors. Differences were identified between Maori and non-Maori in measures of diabetes distress and disordered eating, with Maori more likely to score in clinically significant ranges (50% vs. 19.9%; 53.6% vs. 26.7%, p < 0.05). Disordered eating was correlated with HbA1c , body mass index, and social deprivation; diabetes distress was associated with HbA1c and inversely with age (all p < 0.05). CONCLUSIONS: This study is the first of its kind to determine that New Zealanders living with T1D experience significant psychological distress. Research with larger Maori representation is needed to more closely review identified inequities. Replication in other local clinics will help contribute to the ongoing development of normative data for Aotearoa New Zealand.

Comparing Two Treatment Approaches for Patients with Type 1 Diabetes During Aerobic Exercise: a Randomised, Crossover Study.

BACKGROUND: In a randomised, counterbalanced, crossover design, eight men with type 1 diabetes (T1D; mean ± SD age, 27.6 ± 11.4 years) reduced insulin (INS) by 50% of their normal dose or consumed carbohydrates equivalent to 1 g of carbohydrate per kilogramme of their body weight without the usual insulin bolus (CARBS) over two sessions, held a week apart. Each session included standardised meals, a 45-min treadmill walk at 7.24 km h-1 and a 6-min walk test (6MWT). Rate of perceived exertion (RPE), blood glucose, ketone and lactate measures were taken before, during and immediately after the aerobic exercise. The distance covered in metres and the predicted VO2 max (mL kg-1 min-1) were also calculated for the 6MWT. RESULTS: Participants completing the INS intervention spent more time in normoglycaemia (242 ± 135 min vs 88 ± 132 min; P < 0.01) and less time in hyperglycaemia (41 ± 95 min vs 154 ± 125 min; P = 0.01) as compared to the CARBS intervention. Mild hypoglycaemia occurred in two participants during INS and no participants during CARBS. Furthermore, there was no significant difference for blood lactate, ketone, RPE, distance covered and predicted VO2 max between interventions. CONCLUSION: Based on this pilot study, INS intervention appears to be the best approach for maintaining blood glucose levels in those with T1D during aerobic exercise, though this does need evaluation in other groups, including women, children and those with suboptimal glycaemic control. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12619001397101p . Registered 09 September 2019.

The clinical workforce caring for emerging adults with diabetes in New Zealand is under resourced.

Diabetes is one of the most common chronic disorders in emerging adults (15-25 years of age), and the prevalence of both type 1 diabetes (T1D) and type 2 diabetes (T2D) in New Zealand continues to increase in this age group. Tight glycaemic control in both T1D and T2D is well known to reduce diabetic microvascular and macrovascular complications and improve survival. However, in New Zealand and worldwide, emerging adulthood is typically the period of worst glycaemic control in the lifespan due to the high prevalence of psychosocial stressors and increased insulin resistance of puberty and risk-taking behaviours. In addition, the glycaemic control of emerging adults with diabetes in New Zealand often deteriorates due to the loss of support from family and friends from moving regions, the failure of support from paediatric services to extend to emerging adulthood and the loss of public funding for insulin pump therapy as glycaemic targets are no longer met. Given the high prevalence of psychosocial stressors and the loss of support, the International Society for Paediatric and Adolescent Diabetes's (ISPAD's) guidelines recommend that emerging adults with diabetes receive ambulatory care from a dedicated multidisciplinary team consisting of 0.75 full time equivalent (FTE)/100 patients of an endocrinologist, 1-1.25 FTE/100 patients of a diabetes nurse specialist, 0.5 FTE/100 patients of a dietitian, 0.3 FTE/100 patients of a psychologist and 0.3 FTE/100 patients of a social worker or youth worker.

Glycaemic control across the lifespan in a cohort of New Zealand patients with type 1 diabetes mellitus.

BACKGROUND: It is well known that tight glycaemic control reduces all-cause mortality and the development of microvascular complications in patients with type 1 diabetes mellitus (T1D), but that effective glycaemic control is difficult to achieve in different age groups. Currently, the state of glycaemic control across the lifespan in patients with T1D in New Zealand is not known. AIM: To determine the differences in glycaemic control with age, gender, rurality and ethnicity in patients with T1D in the Waikato region of New Zealand. METHODS: Retrospective review of clinical records of all patients with T1D on the Waikato Regional Diabetes Database in December 2017 (n = 1303). Glycaemic control was determined by the most recent HbA1c in the past 2 years. RESULTS: Median (25%, 75%) HbA1c was 67 (59, 81) mmol/mol (8.3%) and highest in those aged 15-29 years. Values exceeded clinical recommendations in 85.3% of all patients. Median HbA1c was lower in patients on insulin pump therapy than on multiple daily injections (63 (7.9%) versus 69 mmol/mol (8.5%); P < 0.001), though insulin pumps were significantly less likely to be used by Maori (P = 0.003) and men (P < 0.0001). Worsening glycaemic control was associated with increasing social deprivation (P < 0.001) but was not influenced by rural/urban living. CONCLUSIONS: Poor glycaemic control in Waikato patients with T1D is likely due to inequities in health care, including reduced access to insulin pump therapy, particularly in Maori and socially deprived populations.

The prevalence of microvascular complications in Waikato children and youth with type 1 diabetes has reduced since 2003.

AIMS: To determine whether glycaemic control and the prevalence of microvascular complications in Waikato children/youth with type 1 diabetes (T1D) has changed since 2003. METHODS: A retrospective review was performed of clinical records of children and youth with T1D who were under the care of the Waikato Paediatric and Young Adult Diabetes Services between March 2016 and March 2017. Comparisons were made to published data from the same service in 2003. RESULTS: Despite a more than two-fold increase in insulin-pump therapy since 2003, glycaemic control was not significantly improved in either children or youth. However, since 2003 there has been a significant reduction in the prevalence of diabetic retinopathy (24.6% vs 6.0%; P=0.003) and nephropathy (6.0% vs 25.4%; P=0.002), while symptomatic diabetic neuropathy remains rare. This reduction occurred despite a significant increase in obesity and hypertension, and no significant difference in the rates of dyslipidaemia or smoking. CONCLUSIONS: There has been a marked reduction in microvascular complications in Waikato youth and young adults with type 1 diabetes, but the reasons for the reduction are not clear given there has been no significant improvements in glycaemic control.

Glycemic-aware metrics and oversampling techniques for predicting blood glucose levels using machine learning.

Techniques using machine learning for short term blood glucose level prediction in patients with Type 1 Diabetes are investigated. This problem is significant for the development of effective artificial pancreas technology so accurate alerts (e.g. hypoglycemia alarms) and other forecasts can be generated. It is shown that two factors must be considered when selecting the best machine learning technique for blood glucose level regression: (i) the regression model performance metrics being used to select the model, and (ii) the preprocessing techniques required to account for the imbalanced time spent by patients in different portions of the glycemic range. Using standard benchmark data, it is demonstrated that different regression model/preprocessing technique combinations exhibit different accuracies depending on the glycemic subrange under consideration. Therefore technique selection depends on the type of alert required. Specific findings are that a linear Support Vector Regression-based model, trained with normal as well as polynomial features, is best for blood glucose level forecasting in the normal and hyperglycemic ranges while a Multilayer Perceptron trained on oversampled data is ideal for predictions in the hypoglycemic range.

Regulation of murine skeletal muscle growth by STAT5B is age- and sex-specific.

BACKGROUND: Sexually dimorphic growth has been attributed to the growth hormone (GH)/insulin-like growth factor 1 (IGF1) axis, particularly GH-induced activation of the intracellular signal transducer and activator of transcription 5B (STAT5B), because deletion of STAT5B reduces body mass and the mass of skeletal muscles in male mice to that in female mice. However, it remains unclear why these effects are sex- and species-specific, because the loss of STAT5B retards growth in girls, but not in male mice. Our objectives were to determine whether sexually dimorphic growth of skeletal muscle persisted in STAT5B-/- mice and investigate the mechanisms by which STAT5B regulates sexually dimorphic growth. METHODS: Blood and skeletal muscle were harvested from male and female STAT5B-/- mice and their wild-type littermates from the onset of puberty to adulthood. RESULTS: Growth of the skeleton and skeletal muscles was retarded in both sexes of STAT5B-/- mice, but more so in males. Although reduced, sexually dimorphic growth of skeletal muscle persisted in STAT5B-/- mice with an oxidative shift in the composition of myofibres in both sexes. Concentrations of IGF1 in blood and skeletal muscle were reduced in male STAT5B-/- mice at all ages, but only in female STAT5B-/- mice at the onset of puberty. Expression of androgen receptor (AR) and oestrogen receptor alpha (ERα) mRNA and protein was reduced in skeletal muscles of male and female STAT5B-/- mice, respectively. Loss of STAT5B abolished the sexually dimorphic expression of myostatin protein and Igf1, Ar, Erα, suppressor of cytokine signalling 2 (Socs2), and cytokine-inducible SH2-containing protein (Cis) mRNA in skeletal muscle. CONCLUSIONS: STAT5B appears to mediate GH signalling in skeletal muscles of male mice at all ages, but only until puberty in female mice. STAT5B also appears to mediate the actions of androgens and oestrogens in both male and female mice, but sexually dimorphic growth persists in STAT5B-/- mice.

GH replacement titrated to serum IGF-1 does not reduce concentrations of myostatin in blood or skeletal muscle.

OBJECTIVE: Traditional weight-based regimens of GH replacement are more effective at reversing the loss of skeletal muscle in GH-deficient adults than currently recommended regimens, where the dose of GH is increased to restore serum concentrations of IGF-1. While weight-based regimens increase concentrations of IGF-1 and decrease concentrations of myostatin, it is not known whether the reduced effectiveness of individually titrated GH regimens is due to ongoing hypersecretion of myostatin. Consequently, the aims of this study were to determine whether concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults, and whether these concentrations are decreased by GH replacement regimens titrated to restore serum IGF-1. DESIGN: Twenty-six GH deficient adults (18 men and 8 women) were treated with individualised regimens of recombinant human GH aiming to achieve serum concentrations of IGF-1 within one standard deviation of the age- and gender-adjusted mean. Plasma concentrations of myostatin were measured at baseline and after 6 months of treatment were compared to fifteen healthy controls (9 men and 6 women). Skeletal muscle biopsies were performed in 19 of these GH-deficient adults (15 men and 4 women) and 10 of the healthy controls (6 men and 4 women). Expression of IGF-1 and myostatin mRNA was determined by qPCR. RESULTS: Concentrations of IGF-1 in serum and mRNA in skeletal muscle were reduced, and concentrations of myostatin in plasma and mRNA in skeletal muscle were increased in GH-deficient adults at baseline (P < .05 versus healthy controls). Despite restoring concentrations of IGF-1, GH replacement did not reduce concentrations of myostatin in either blood or skeletal muscle. Concentrations of IGF-1 and myostatin in both blood and skeletal muscle were positively correlated in GH-deficient adults at baseline (P < .05), but not in GH-replete adults. CONCLUSIONS: Concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults. Despite normalising concentrations of IGF-1, individualised regimens of GH replacement do not reduce concentrations of myostatin in blood or skeletal muscle. Ongoing hypersecretion of myostatin may explain why individually titrated GH replacement regimens are less effective than higher weight-based regimens in increasing skeletal muscle mass.

Retrospective investigation of testosterone undecanoate depot for the long-term treatment of male hypogonadism in clinical practice.

INTRODUCTION: Testosterone undecanoate depot (TUD) administered intramuscularly is an effective form of testosterone replacement therapy (TRT) for male hypogonadism. Because of the ease of administration, TUD therapy may be preferable to subcutaneously implanted extended release T pellet implants (TI). AIM: The primary objective was to retrospectively assess the efficacy and safety of long-term (≥ 2 years therapy) TUD therapy in the clinical setting. The secondary objective was to retrospectively compare TUD with TI therapy. METHODS: Retrospective data were collected from the Waikato Hospital Endocrine Database for 179 hypogonadal men treated with TUD for ≥ 2 years from 1998-2011, with 124 of these men receiving previous TI therapy. MAIN OUTCOME MEASURES: The main outcome measure for efficacy was serum trough total testosterone (TT), and for safety an increase in hemoglobin (Hb) and/or hematocrit (Hct), rise in prostate-specific antigen (PSA) and/or prostatic biopsy and alteration in body mass index and lipid profile. Additional outcome measures were changes in the dosing and/or interval regimens for TUD therapy. RESULTS: Overall, 72% of trough TT levels were in the normal range for TUD therapy compared with 53% of trough TT levels during TI therapy. TUD therapy was well tolerated with 162 men (90.5%) completing 2 years of treatment, and only seven men (3.9%) stopping TUD because of adverse effects. A rise in Hb and/or Hct occurred in 25 men (14%), and a significant rise in PSA in 20 men (13%) at some stage during TUD therapy. At 2 years, 91% of men received the standard 1,000 mg TUD dose with 66% at the standard dosing interval of 10-14 weekly. CONCLUSIONS: TUD is an efficacious, safe, and well tolerated form of TRT, and individual optimisation of the dose and/or interval is only required in the minority of men. Particularly given the ease of administration, TUD was the preferred TRT for both patients and clinicians.