Early feasibility study with an implantable near-infrared spectroscopy sensor for glucose, ketones, lactate and ethanol.

OBJECTIVE: To evaluate the safety and performance of an implantable near-infrared (NIR) spectroscopy sensor for multi-metabolite monitoring of glucose, ketones, lactate, and ethanol. RESEARCH DESIGN AND METHODS: This is an early feasibility study (GLOW, NCT04782934) including 7 participants (4 with type 1 diabetes (T1D), 3 healthy volunteers) in whom the YANG NIR spectroscopy sensor (Indigo) was implanted for 28 days. Metabolic challenges were used to vary glucose levels (40-400 mg/dL, 2.2-22.2 mmol/L) and/or induce increases in ketones (ketone drink, up to 3.5 mM), lactate (exercise bike, up to 13 mM) and ethanol (4-8 alcoholic beverages, 40-80g). NIR spectra for glucose, ketones, lactate, and ethanol levels analyzed with partial least squares regression were compared with blood values for glucose (Biosen EKF), ketones and lactate (GlucoMen LX Plus), and breath ethanol levels (ACE II Breathalyzer). The effect of potential confounders on glucose measurements (paracetamol, aspartame, acetylsalicylic acid, ibuprofen, sorbitol, caffeine, fructose, vitamin C) was investigated in T1D participants. RESULTS: The implanted YANG sensor was safe and well tolerated and did not cause any infectious or wound healing complications. Six out 7 sensors remained fully operational over the entire study period. Glucose measurements were sufficiently accurate (overall mean absolute (relative) difference MARD of 7.4%, MAD 8.8 mg/dl) without significant impact of confounders. MAD values were 0.12 mM for ketones, 0.16 mM for lactate, and 0.18 mM for ethanol. CONCLUSIONS: The first implantable multi-biomarker sensor was shown to be well tolerated and produce accurate measurements of glucose, ketones, lactate, and ethanol. TRIAL REGISTRATION: Clinical trial identifier: NCT04782934.

Functional insulin therapy in type 1 diabetics: Short-term effects on weight and nutritional intake.

INTRODUCTION-AIM: Flexible insulin therapy is currently considered the gold standard therapy of type 1 diabetes. We aimed to study the evolution of glycemic control, weight and nutritional intake of a group of patients with type 1 diabetes, three months after the initiation of functional insulin therapy (FIT). METHODS: This was a prospective longitudinal study having included 30 type 1 diabetic patients hospitalized for education to FIT. Each patient underwent an assessment of glycemic control (glycated hemoglobin (A1C) and number of hypoglycemia), weight and nutritional intake before FIT and 3 months after the initiation of this educative approach. RESULTS: The mean age of patients was 21,8 ± 7,9 years and the sex ratio was 0,5. The mean duration of diabetes was 7,2 ± 6 years. Three months after initiation of FIT, we observed a significant lowering of A1C, which went from 9,2 ± 1,6% to 8,3 ± 1,4% (p<0,001) of the number of minor hypoglycemia (p=0,001) and that of severe hypoglycemia (p= 0,021). the average weight went from 64,6 ± 13,1 kg to 65,5 ± 13,5 kg (p = 0,040) with a significant increase in BMI (p = 0,041). Weight gain was observed in 67% of patients. This weight gain contrasted with a significant decrease in caloric (p = 0,040) and in carbohydrates intakes (p = 0,027). CONCLUSION: Weight gain, associated with better glycemic control, should encourage the healthcare team to strengthen therapeutic education of patients undergoing FIT in order to limit weight gain.

Appropriateness and acceptability of continuous glucose monitoring in people with type 1 diabetes at rural first-level hospitals in Malawi: a qualitative study.

OBJECTIVES: The purpose of this qualitative study is to describe the acceptability and appropriateness of continuous glucose monitoring (CGM) in people living with type 1 diabetes (PLWT1D) at first-level (district) hospitals in Malawi. DESIGN: We conducted semistructured qualitative interviews among PLWT1D and healthcare providers participating in the study. Standardised interview guides elicited perspectives on the appropriateness and acceptability of CGM use for PLWT1D and their providers, and provider perspectives on the effectiveness of CGM use in Malawi. Data were coded using Dedoose software and analysed using a thematic approach. SETTING: First-level hospitals in Neno district, Malawi. PARTICIPANTS: Participants were part of a randomised controlled trial focused on CGM at first-level hospitals in Neno district, Malawi. Pretrial and post-trial interviews were conducted for participants in the CGM and usual care arms, and one set of interviews was conducted with providers. RESULTS: Eleven PLWT1D recruited for the CGM randomised controlled trial and five healthcare providers who provided care to participants with T1D were included. Nine PLWT1D were interviewed twice, two were interviewed once. Of the 11 participants with T1D, six were from the CGM arm and five were in usual care arm. Key themes emerged regarding the appropriateness and effectiveness of CGM use in lower resource setting. The four main themes were (a) patient provider relationship, (b) stigma and psychosocial support, (c) device usage and (d) clinical management. CONCLUSIONS: Participants and healthcare providers reported that CGM use was appropriate and acceptable in the study setting, although the need to support it with health education sessions was highlighted. This research supports the use of CGM as a component of personalised diabetes treatment for PLWT1D in resource constraint settings. TRIAL REGISTRATION NUMBER: PACTR202102832069874; Post-results.

Feasibility of continuous glucose monitoring in patients with type 1 diabetes at two district hospitals in Neno, Malawi: a randomised controlled trial.

OBJECTIVES: To assess the feasibility and change in clinical outcomes associated with continuous glucose monitoring (CGM) use among a rural population in Malawi living with type 1 diabetes. DESIGN: A 2:1 open randomised controlled feasibility trial. SETTING: Two Partners In Health-supported Ministry of Health-run first-level district hospitals in Neno, Malawi. PARTICIPANTS: 45 people living with type 1 diabetes (PLWT1D). INTERVENTIONS: Participants were randomly assigned to Dexcom G6 CGM (n=30) use or usual care (UC) (n=15) consisting of Safe-Accu glucose monitors and strips. Both arms received diabetes education. OUTCOMES: Primary outcomes included fidelity, appropriateness and severe adverse events. Secondary outcomes included change in haemoglobin A1c (HbA1c), acceptability, time in range (CGM arm only) SD of HbA1c and quality of life. RESULTS: Participants tolerated CGM well but were unable to change their own sensors which resulted in increased clinic visits in the CGM arm. Despite the hot climate, skin rashes were uncommon but cut-out tape overpatches were needed to secure the sensors in place. Participants in the CGM arm had greater numbers of dose adjustments and lifestyle change suggestions than those in the UC arm. Participants in the CGM arm wore their CGM on average 63.8% of the time. Participants in the UC arm brought logbooks to clinic 75% of the time. There were three hospitalisations all in the CGM arm, but none were related to the intervention. CONCLUSIONS: This is the first randomised controlled trial conducted on CGM in a rural region of a low-income country. CGM was feasible and appropriate among PLWT1D and providers, but inability of participants to change their own sensors is a challenge. TRIAL REGISTRATION NUMBER: PACTR202102832069874.

Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?

BACKGROUND: Insulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes. METHODS: The baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status. RESULTS: In 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status. CONCLUSIONS: In type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.

Integrated analysis of blood DNA methylation, genetic variants, circulating proteins, microRNAs, and kidney failure in type 1 diabetes.

Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5'-cytosine-phosphate-guanine-3' loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at P = 6.62 × 10-14. In conclusion, our multiomics study provides insights into mechanisms through which variation of DNAmet may affect KF development and shows that blood cell DNAmet at certain CpGs can improve risk prediction for KF in T1D.

Continuous Glucose Monitoring Is Associated with Lower Risk of Diabetic Retinopathy.

According to this study: In adults with type 1 diabetes, continuous glucose monitoring (CGM) was associated with lower odds of developing diabetic retinopathy and proliferative diabetic retinopathy.No associations were found between CGM use, insulin pump use, or the use of both CGM and an insulin pump with progression of diabetic retinopathy.

Enhancing equity in access to automated insulin delivery systems in an ethnically and socioeconomically diverse group of children with type 1 diabetes.

INTRODUCTION: Manufacturer-supported didactic teaching programmes offer effective automated insulin delivery (AID) systems onboarding in children and young people (CYP) with type 1 diabetes (T1D). However, this approach has limited flexibility to accommodate the needs of families requiring additional support. RESEARCH DESIGN AND METHODS: Evaluate the efficacy of an inperson manufacturer-supported didactic teaching programme (Group A), in comparison to a flexible flipped learning approach delivered virtually or inperson (Group B). Retrospective analysis of CYP with T1D using continuous glucose monitoring (CGM), who were initiated on AID systems between 2021 and 2023. Compare CGM metrics from baseline to 90 days for both groups A and B. Additionally, compare the two groups for change in CGM metrics over the 90-day period (∆), patient demographics and onboarding time. RESULTS: Group A consisted of 74 CYP (53% male) with median age of 13.9 years and Group B 91 CYP (54% male) with median age of 12.7 years. From baseline to 90 days, Group A lowered mean (±SD) time above range (TAR, >10.0 mmol/L) from 47.6% (±15.0) to 33.2% (±15.0) (p<0.001), increased time in range (TIR, 3.9-10.0 mmol/L) from 50.4% (±14.0) to 64.7% (±10.2) (p<0.001). From baseline to 90 days, Group B lowered TAR from 51.3% (±15.1) to 34.5% (±11.3) (p<0.001) and increased TIR from 46.5% (±14.5) to 63.7% (±11.0) (p<0.001). There was no difference from baseline to 90 days for time below range (TBR, <3.9 mmol/L) for Group A and Group B. ∆ TAR, TIR and TBR for both groups were comparable. Group B consisted of CYP with higher socioeconomic deprivation, greater ethnic diversity and lower carer education achievement (p<0.05). The majority of Group B (n=79, 87%) chose virtual flipped learning, halving diabetes educator time and increasing onboarding cadence by fivefold. CONCLUSIONS: A flexible virtual flipped learning programme increases onboarding cadence and capacity to offer equitable AID system onboarding.

Prematurity and congenital malformations differ according to the type of pregestational diabetes.

BACKGROUND: Diabetes mellitus (DM) is the most common metabolic disorder in pregnancy. Women with Type 2 DM seems to have no better perinatal outcomes than those with Type 1 DM. METHODS: Single-center prospective cohort observational study. Pregnant women with diabetes (141 with Type 1 DM and 124 with Type 2 DM) that were followed in the university hospital between 2009 and 2021 were included in this study. Clinical data and obstetric and perinatal outcomes were collected. RESULTS: As expected, women with Type 1 DM were younger and had a longer duration of diabetes than women with Type 2 DM. Obesity and chronic hypertension were higher in the group of women with Type 2 DM and their value of HbA1c in the second and third trimesters were lower than in Type 1 DM. No differences in prematurity were found, but more extreme prematurity was observed in Type 2 DM, as well as a higher rate of congenital malformations. The frequency of hypoglycemia and the weight of the newborn was higher in Type 1 DM. The maternal independent factors related to the weight of the newborn were: the glycemic control at the third trimester, the weight gain during pregnancy, and pregestational BMI. CONCLUSIONS: Newborns born to mothers with Type 1 DM were larger and had a higher frequency of hypoglycemia, while congenital malformations and precocious preterm was more associated to Type 2 DM. Metabolic control, weight gain and pregestational weight were important determinants of both obstetric and neonatal complications.

Effects of Dietary Carbohydrate Concentration and Glycemic Index on Blood Glucose Variability and Free Fatty Acids in Individuals with Type 1 Diabetes.

Monitoring glycemic control status is the cornerstone of diabetes management. This study aimed to reveal whether moderate-carbohydrate (CHO) diets increase the risk of free fatty acid (FFA) levels, and it presents the short-term effects of four different diet models on blood sugar, glycemic variability (GV), and FFA levels. This crossover study included 17 patients with type 1 diabetes mellitus to identify the effects of four diets with different CHO contents and glycemic index (GI) on GV and plasma FFA levels. Diet 1 (D1) contained 40% CHO with a low GI, diet 2 (D2) contained 40% CHO with a high GI, diet 3 (D3) contained 60% CHO with a low GI, and diet 4 (D4) contained 60% CHO with a high GI. Interventions were performed with sensor monitoring in four-day periods and completed in four weeks. No statistical difference was observed among the groups in terms of blood glucose area under the curve (p = 0.78), mean blood glucose levels (p = 0.28), GV (p = 0.59), and time in range (p = 0.567). FFA and total triglyceride levels were higher in the D1 group (p < 0.014 and p = 0.002, respectively). Different diets may increase the risk of cardiovascular diseases by affecting GI, FFA, and blood glucose levels.

Implementation research: a protocol for two three-arm pragmatic randomised controlled trials on continuous glucose monitoring devices in people with type 1 diabetes in South Africa and Kenya.

BACKGROUND: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. METHODS: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). DISCUSSION: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. TRIAL REGISTRATION: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.

Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial.

BACKGROUND: Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. METHODS: CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971). FINDINGS: Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. INTERPRETATION: In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. FUNDING: Diabetes Liga Research Fund and Medtronic.

Association Between Treatment Adherence and Continuous Glucose Monitoring Outcomes in People With Diabetes Using Smart Insulin Pens in a Real-World Setting.

OBJECTIVE: To evaluate the association of insulin injection adherence, smart insulin pen engagement, and glycemic control using real-world data from 16 countries from adults self-administering basal insulin degludec and bolus insulin with a smart insulin pen (NovoPen 6 or NovoPen Echo Plus) alongside continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS: Data were aggregated over 14-day periods. Treatment adherence was defined according to the number of missed basal and missed bolus insulin doses and smart pen engagement according to the number of days with data uploads. RESULTS: Data from 3,945 adults, including 25,157 14-day periods with ≥70% CGM coverage, were analyzed. On average, 0.2 basal and 6.0 bolus insulin doses were missed over 14 days. The estimated probability of missing at least one basal insulin dose over a 14-day period was 17.6% (95% CI 16.5, 18.7). Missing one basal or bolus insulin dose per 14 days was associated with a significant decrease in percentage of time with glucose levels in range (TIR) (3.9-10.0 mmol/L), of -2.8% (95% CI -3.7, -1.8) and -1.7% (-1.8, -1.6), respectively; therefore, missing two basal or four bolus doses would decrease TIR by >5%. Smart pen engagement was associated positively with glycemic outcomes. CONCLUSIONS: This combined analysis of real-world smart pen and CGM data showed that missing two basal or four bolus insulin doses over a 14-day period would be associated with a clinically relevant decrease in TIR. Smart insulin pens provide valuable insights into treatment injection behaviors.

Sustained Effectiveness of an Advanced Hybrid Closed-Loop System in a Cohort of Children and Adolescents With Type 1 Diabetes: A 1-Year Real-World Study.

OBJECTIVE: To investigate glucose metrics and identify potential predictors of the achievement of glycemic outcomes in children and adolescents during their first 12 months of MiniMed 780G use. RESEARCH DESIGN AND METHODS: This multicenter, longitudinal, real-world study recruited 368 children and adolescents with type 1 diabetes (T1D) starting SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months. The influence of covariates on glycemic outcomes after 1 year of MiniMed 780G use was assessed. RESULTS: After 15 days of automatic mode use, all glucose metrics improved compared with baseline (P < 0.001), except for time below range (P = 0.113) and coefficient of variation (P = 0.330). After 1 year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P < 0.001). The mean glycated hemoglobin (HbA1c) over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P < 0.001). Time spent in tight range (70-140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with a reduced number of automatic correction boluses (P < 0.001), fewer SmartGuard exits (P = 0.021), and longer time in automatic mode (P = 0.030). Individuals with baseline HbA1c >8% showed more relevant improvement in TIR levels (from 54.3% to 72.3%). CONCLUSIONS: Our study highlights the sustained effectiveness of MiniMed 780G among youth with T1D. Findings suggest that even children and adolescents with low therapeutic engagement may benefit from SmartGuard technology.

Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Long-term assessment of the NHS hybrid closed-loop real-world study on glycaemic outcomes, time-in-range, and quality of life in children and young people with type 1 diabetes.

Hybrid closed-loop (HCL) systems seamlessly interface continuous glucose monitoring (CGM) with insulin pumps, employing specialised algorithms and user-initiated automated insulin delivery. This study aimed to assess the efficacy of HCLs at 12 months post-initiation on glycated haemoglobin (HbA1c), time-in-range (TIR), hypoglycaemia frequency, and quality of life measures among children and young people (CYP) with type 1 diabetes mellitus (T1DM) and their caregivers in a real-world setting. Conducted between August 1, 2021, and December 10, 2022, the prospective recruitment took place in eight paediatric diabetes centres across England under the National Health Service England's (NHSE) HCL pilot real-world study. A cohort of 251 CYP (58% males, mean age 12.3 years) with T1DM participated (89% white, 3% Asian, 4% black, 3% mixed ethnicity, and 1% other). The study utilised three HCL systems: (1) Tandem Control-IQ AP system, which uses the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, San Diego, CA, USA) with the Dexcom G6® CGM (Dexcom, San Diego, CA, USA) sensor; (2) Medtronic MiniMed™ 780G with the Guardian 4 sensor (Medtronic, Northridge, CA, USA); and (3) the CamAPS FX (CamDiab, Cambridge, UK) with the Ypsomed insulin pump (Ypsomed Ltd, Escrick, UK) and Dexcom G6® CGM.All systems were fully funded by the NHS. Results demonstrated significant improvements in HbA1c (average reduction at 12 months 7 mmol/mol; P < 0.001), time-in-range (TIR) (average increase 13.4%; P < 0.001), hypoglycaemia frequency (50% reduction), hypoglycaemia fear, and quality of sleep (P < 0.001) among CYP over a 12-month period of HCL usage. Additionally, parents and carers experienced improvements in hypoglycaemia fear and quality of sleep after 6 and 12 months of use. In addition to the improvements in glycaemic management, these findings underscore the positive impact of HCL systems on both the well-being of CYP with T1DM and the individuals caring for them.

Serum testosterone levels and oxidative stress in type 1 diabetes, type 2 diabetes, and obesity.

INTRODUCTION: Obesity, type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) are metabolic diseases that continue to be a global problem. Testosterone levels in men are affected by several factors, including obesity and DM. Although the relationship between diabetes and testosterone is not fully understood, oxidative stress is thought to play a major role. The aim of this study was to compare serum testosterone levels and oxidative stress markers [total antioxidant status (TAS), total oxidant capacity (TOS), oxidative stress index (OSI), and ischaemic modified albumin (IMA)] among the control group and experimentally induced obese, T1DM, and T2DM rats. MATERIAL AND METHODS: The study included 28 male Sprague-Dawley rats divided into 4 groups: the obesity group were fed a high-fat diet (HFD), the T2DM group received a HFD plus a single dose of streptozocin (STZ), the T1DM group received only STZ, and there was a control group. Serum testosterone, TAS, TOS, OSI, and IMA were analysed. RESULTS: Serum testosterone levels were lower in the T1DM and T2DM groups compared to the control and obesity groups. The TOS levels were highest in the T2DM group, followed by the T1DM group, the obesity group, and finally the control group. No significant difference was found between the obesity group and the control group in terms of TOS levels. Regarding TAS levels, the order observed was control group > obesity group > T2DM > T1DM. Testosterone was positively correlated with TAS and negatively correlated with TOS and OSI. CONCLUSIONS: Increased oxidative stress in diabetes may be an important factor that decreases serum testosterone levels.

Continuous subcutaneous insulin infusion versus multiple daily injection therapy in pregnant women with type 1 diabetes.

INTRODUCTION: The study aimed to compare glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) using multiple daily injection therapy (MDI) and continuous subcutaneous insulin infusion (CSII) and to compare outcomes of women treated with long-acting insulin or neutral protamine Hagedorn (NPH). METHODS: This multicenter prospective cohort study involved women with pregestational T1DM treated with MDI and CSII. Primary outcome was glycated hemoglobin (HbA1c) before and during pregnancy. Secondary outcomes included maternal and neonatal outcomes and quality of life. RESULTS: Of the 121 studied women, the average age was 28.48 years, and the average body mass index was 21.29 kg/m2 at conception and 26.32 kg/m2 at delivery. Of the studied women, 78.51% had planned pregnancy. Women treated with MDI and CSII had comparable HbA1c before pregnancy or in the first and second trimesters. In the third trimester, women on CSII therapy had significantly lower HbA1c (6.07 ± 0.62 vs 6.20 ± 0.88%, p = .017), higher HbA1c on-target rate (71.43% vs 64.62%, p = .030), and greater decline of HbA1c from preconception to the third trimester (-0.65 vs -0.30%, p = .047). Fewer daily insulin requirements were observed in those used CSII compared with MDI-treated women (0.60 ± 0.22 vs 0.73 ± 0.25 U/kg/day, p = .004). Newborns born of mothers treated with the CSII method were more likely to have neonatal jaundice (adjusted odds ratio [OR] 2.76, 95% confidence interval [CI] 1.16-6.57) and neonatal intensive care unit (adjusted OR 3.73, 95%CI 1.24-11.16), and women on CSII had lower scores in patient-reported quality of life (p = .045). In the MDI group, those receiving long-acting insulin had nonsignificant lower HbA1c and higher HbA1c on-target rate in the second and third trimesters, compared with those treated with NPH. CONCLUSIONS: Insulin pump users may achieve better glycemic control than multiple daily insulin injections, which did not substantially improve pregnancy outcome.

Short, frequent, light-intensity walking activity improves postprandial vascular-inflammatory biomarkers in people with type 1 diabetes: The SIT-LESS randomized controlled trial.

AIM: To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. RESULTS: Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1ß, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1ß, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1ß (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. CONCLUSIONS: Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN13641847).

Changes in glucometric parameters in people living with diabetes users of the free-style libre 2 system before and after the update possibility to real-time glucose readings in real world practice.

In Spain, from October 10th, 2023, the FreeStyle Libre 2 system offers the possibility to automatically changed from isCGM to rtCGM with a system update. Our study aimed to evaluate the glucometric before and after that date. We didn't find significant changes in TIR, however time of use increased and TBR decreased.