Beneficial effects of automated insulin delivery over one-year follow-up in real life for youths and adults with type 1 diabetes irrespective of patient characteristics.

AIM: To investigate glycaemic outcomes in youths and adults with type 1 diabetes with either MiniMed™ 780G or Tandem t:slim X2™ control-IQ automated insulin delivery (AID) systems and to evaluate clinical factors that migrate, mitigate the achievement of therapeutic goals. MATERIALS AND METHODS: This retrospective, real-world, observational study was conducted in a specialized university type 1 diabetes centre with patients observed for 3-12 months post-initiation of an AID system. Primary outcomes were the percentage time in the target glucose range [TIR70-180 mg/dl (3.9-10 mmol/L)] as measured by continuous glucose monitoring, mean glucose management indicator (GMI) and glycated haemoglobin (HbA1c) levels. RESULTS: Our study cohort consisted of 48 adolescents and 183 adults (55% females) aged 10-77 years. The mean (95% confidence interval) TIR70-180 mg/dl after 30 days was higher than baseline and by 14% points after 360 days with 71.33% (69.4-73.2) (n = 123, p < .001). HbA1c levels decreased by 0.7% and GMI by 0.6% after 360 days. The proportion of time spent <70 mg/dl (3.9 mmol/L) was not significantly different from baseline. During follow-up, 780G users had better continuous glucose monitoring results than control-IQ users but similar HbA1c levels, and an increased risk of weight gain. Age at onset influenced TIR70-180 mg/dl in univariate analysis but there was no significant relationship after adjusting on explanatory variables. Baseline body mass index did not influence the performance of AID systems. CONCLUSIONS: This analysis showed the beneficial effects of two AID systems for people with type 1 diabetes across a broad spectrum of participant characteristics. Only half of the participants achieved international recommendations for glucose control with TIR70-180 mg/dl >70%, HbA1c levels or GMI <7%, which outlines the need to maintain strong educational and individual strategies.

Effects of advanced carbohydrate counting on glucose control and quality of life in children with type 1 diabetes.

OBJECTIVE: The effect of advanced carbohydrate counting (ACC) on metabolic and quality of life (QOL) outcomes is uncertain in children with type 1 diabetes. Our aim was to determine whether ACC would improve HbA1c and QOL scores as compared with standard nutrition in this population. METHODS: We randomized 87 patients using pump and rapid-acting analogs in a 1 year randomized multicenter study (age 9.6 ± 3.5 years, diabetes duration 4.6 ± 2.7 years, HbA1c 7.8 ± 0.5% [62 ± 5 mmol/mol]). The ACC group received CC education and the control group received traditional dietary education. HbA1c was measured every 3 months. At 0 and 1 year, general, diabetes-specific, and diet-related QOL were respectively assessed by the KIDSCREEN and WHO-5 questionnaires, the diabetes-specific module of the DISABKIDS, and the diet restriction items of the DSQOLS. RESULTS: Mean HbA1c was lower in the ACC than the control group at 3 months (P < .05) and tended to be lower at 6 months (P = .10), 9 months (P = .10), but not at 12 months. The mean of individual average HbA1c during the one-year study period (from M3 to M12) was 7.63 ± 0.43 in the ACC vs 7.85 ± 0.47% in the control group (60 ± 5 vs 62 ± 5 mmol/mol)(P < .05). ACC was associated with significantly higher scores at 1 year on the KIDSCREEN children's psychological scale and the KIDSCREEN parents' physical scale, the DISABKIDS children's treatment scale, and the children's and parents' dietary restriction scales of the DSQOLS (indicating better QOL or lower perceived diet restriction). CONCLUSIONS: ACC may be associated with small improvements in metabolic control and QOL scores in children.

A systematic review of non-genetic predictors and genetic factors of glycated haemoglobin in type 1 diabetes one year after diagnosis.

Type 1 diabetes (T1D) results from autoimmune destruction of the pancreatic ßcells. Although all T1D patients require daily administration of exogenous insulin, their insulin requirement to achieve good glycaemic control may vary significantly. Glycated haemoglobin (HbA1c) level represents a stable indicator of glycaemic control and is a reliable predictor of long-term complications of T1D. The purpose of this article is to systematically review the role of non-genetic predictors and genetic factors of HbA1c level in T1D patients after the first year of T1D, to exclude the honeymoon period. A total of 1974 articles published since January 2011 were identified and 78 were finally included in the analysis of non-genetic predictors. For genetic factors, a total of 277 articles were identified and 14 were included. The most significantly associated factors with HbA1c level are demographic (age, ethnicity, and socioeconomic status), personal (family characteristics, parental care, psychological traits...) and features related to T1D (duration of T1D, adherence to treatment …). Only a few studies have searched for genetic factors influencing HbA1c level, most of which focused on candidate genes using classical genetic statistical methods, with generally limited power and incomplete adjustment for confounding factors and multiple testing. Our review shows the complexity of explaining HbA1c level variations, which involves numerous correlated predictors. Overall, our review underlines the lack of studies investigating jointly genetic and non-genetic factors and their interactions to better understand factors influencing glycaemic control for T1D patients.

Screening strategies for glucose tolerance abnormalities and diabetes in people with cystic fibrosis.

The increase in life expectancy of patients with cystic fibrosis has come with new comorbidities, particularly diabetes. The gradual development of glucose tolerance abnormalities means that 30 to 40% of adults will be diabetic. Cystic fibrosis-related diabetes is a major challenge in the care of these patients because it is a morbidity and mortality factor at all stages of the disease. Early glucose tolerance abnormalities observed from childhood, before the stage of diabetes, are also associated with a poor pulmonary and nutritional outcome. The long asymptomatic period justifies systematic screening with an annual oral glucose tolerance test from the age of 10 years. However, this strategy does not take into account the new clinical profiles of patients with cystic fibrosis, recent pathophysiological knowledge of glucose tolerance abnormalities, and the emergence of new diagnostic tools in diabetology. In this paper, we summarise the challenges of screening in the current context of new patient profiles - patients who are pregnant, have transplants, or are being treated with fibrosis conductance transmembrane regulator modulators - and put forward an inventory of the various screening methods for cystic fibrosis-related diabetes, including their applications, limitations and practical implications.

Screening of ZnT8 autoantibodies in the diagnosis of autoimmune diabetes in a large French cohort.

AIM OF THE STUDY: Evaluate the added value of screening anti-ZnT8 antibodies (ZnT8A) in addition to the classical anti-GAD (GADA) and anti-IA-2 (IA-2A) antibodies for the diagnosis of type-1 diabetes (T1D) within a large cohort of both children and adults. MATERIALS AND METHODS: Retrospective 2-year study including 516 patients (215 children, 301 adults) who had blood tests at diabetes onset and/or for diabetes classification. ZnT8A, GADA, and IA-2A were analyzed in all samples. RESULTS: Among those individuals included, 142 (28%) were ZnT8A-positive. A total of 228/516 suffered from T1D, of whom 110 (48%) were ZnT8A-positive and 166 (73%) GADA and/or IA-2A positive. When adding ZnT8A to GADA/IA-2A, 184 (81%) patients were positive for ≥1 Ab. Regarding the 122 patients at T1D onset, 75 (61%) were positive for ZnT8A and the proportion of patients with T1D with ≥1 Ab reached 89%. The highest prevalence of ZnT8A was observed in children aged 6-10years. Fourteen of the 124 patients positive for ZnT8A with a known clinical diagnosis suffered from a disease other than T1D. CONCLUSIONS: ZnT8A should be included in routine evaluation at diabetes onset and is a valuable biological marker to classify newly-diagnosed diabetics. The predictive value in our high-risk subjects has to be confirmed.

Lack of association of IL-10 promoter gene variants with type 1 diabetes in a French population.

Although genetic predisposition to type 1 diabetes shows a strong association with human leukocyte antigen (HLA) class II alleles, additional genes may influence the immune process and the progression of beta cell loss. Preliminary reports suggested that IL-10 gene polymorphisms contribute to susceptibility to type 1 diabetes. We analyzed the frequencies of three main variants of the promoter region of the IL-10 gene at the positions -1082, -819, and -592 in a cohort of 358 type 1 diabetic patients representing the same regional population pattern and 519 controls from the same region using an enzyme-linked oligonucleotide sorbent assay. We did not find any statistical association in the entire cohort or after stratification for high-risk HLA-DQ alleles. However, the IL-10 -1082 polymorphism was significantly associated with GAD and IA-2 antibodies at clinical onset. Such polymorphism is known to be associated with the reduction of secreted IL-10 which may support the concept of accelerated Th-1 T-cell reactivity. In conclusion, IL-10 promoter gene variants may contribute, but to a minor extent, to disease susceptibility in juvenile type 1 diabetes and should not be included in the routine genetic screening of high-risk individuals.

A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly.

Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic ß-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) encoding the regulatory subunit of an eIF2α-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation and results in ß-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to ß-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities.