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1.
Endocrinol Diabetes Metab ; 7(3): e473, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38597269

RESUMO

BACKGROUND: Previous meta-analyses have shown mixed results regarding the association between eating disorders (EDs) and type 1 diabetes mellitus (T1DM). Our paper aimed to analyse different EDs and disordered eating behaviours that may be practiced by patients with T1DM. METHODS: A literature search of PubMed, Scopus and Web of Science was conducted on 17 January 2023, using the key terms "T1DM," "Eating Disorders" and "Bulimia." Only observational controlled studies were included. The Revman software (version 5.4) was used for the analysis. RESULTS: T1DM was associated with increased risk of ED compared with nondiabetic individuals (RR = 2.47, 95% CI = 1.84-3.32, p-value < 0.00001), especially bulimia nervosa (RR = 2.80, 95% CI = 1.18-6.65, p-value = 0.02) and binge eating (RR = 1.53, 95% CI = 1.18-1.98, p-value = 0.001). Our analysis has shown that increased risk of ED among T1DM persisted regardless of the questionnaire used to diagnose ED; DM-validated questionnaires (RR = 2.80, 95% CI = 1.91-4.12, p-value < 0.00001) and generic questionnaires (RR = 2.03, 95% CI = 1.27-3.23, p-value = 0.003). Prevalence of insulin omission/misuse was 10.3%; diabetic females demonstrated a significantly higher risk of insulin omission and insulin misuse than diabetic males. CONCLUSION: Our study establishes a significant and clear connection between EDs and T1DM, particularly bulimia and binge eating, with T1DM. Moreover, female diabetics are at higher risk of insulin misuse/omission. Early proactive screening is essential and tailored; comprehensive interventions combining diabetes and ED components are recommended for this population, with referral to a specialised psychiatrist.


Assuntos
Bulimia , Diabetes Mellitus Tipo 1 , Transtornos da Alimentação e da Ingestão de Alimentos , Masculino , Humanos , Feminino , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Bulimia/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Insulina , Insulina Regular Humana
2.
Diabetes Metab Res Rev ; 40(2): e3770, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38450851

RESUMO

Diagnosis and management of type 1 diabetes (T1D) have remained largely unchanged for the last several years. The management of the disease remains primarily focused on its phenotypical presentation and less on endotypes, namely the specific biological mechanisms behind the development of the disease. Furthermore, the treatment of T1D is essentially universal and indiscriminate-with patients administering insulin at varying dosages and frequencies to maintain adequate glycaemic control. However, it is now well understood that T1D is a heterogeneous disease with many different biological mechanisms (i.e. endotypes) behind its complex pathophysiology. A range of factors, including age of onset, immune system regulation, rate of ß-cell destruction, autoantibodies, body weight, genetics and the exposome are recognised to play a role in the development of the condition. Patients can be classified into distinct diabetic subtypes based on these factors, which can be used to categorise patients into specific endotypes. The classification of patients into endotypes allows for a greater understanding of the natural progression of the disease, giving rise to more accurate and patient-centred therapies and follow-up monitoring, specifically for other autoimmune diseases. This review proposes 6 unique endotypes of T1D based on the current literature. The recognition of these endotypes could then be used to direct therapeutic modalities based on patients' individual pathophysiology.


Assuntos
Doenças Autoimunes , Diabetes Mellitus Tipo 1 , Humanos , Insulina Regular Humana , Autoanticorpos , Peso Corporal
3.
BMJ Open Diabetes Res Care ; 12(2)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38471670

RESUMO

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants. RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test. RESULTS: Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs). CONCLUSIONS: Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Humanos , Hipoglicemiantes/uso terapêutico , Variantes Farmacogenômicos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/uso terapêutico , Frequência do Gene , Insulina Regular Humana
4.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473764

RESUMO

Inhibition of insulin-regulated aminopeptidase (IRAP) has been shown to improve cognitive functions in several animal models. Recently, we performed a screening campaign of approximately 10,000 compounds, identifying novel small-molecule-based compounds acting as inhibitors of the enzymatic activity of IRAP. Here we report on the chemical synthesis, structure-activity relationships (SAR) and initial characterization of physicochemical properties of a series of 48 imidazo [1,5-α]pyridine-based inhibitors, including delineation of their mode of action as non-competitive inhibitors with a small L-leucine-based IRAP substrate. The best compound displays an IC50 value of 1.0 µM. We elucidate the importance of two chiral sites in these molecules and find they have little impact on the compound's metabolic stability or physicochemical properties. The carbonyl group of a central urea moiety was initially believed to mimic substrate binding to a catalytically important Zn2+ ion in the active site, although the plausibility of this binding hypothesis is challenged by observation of excellent selectivity versus the closely related aminopeptidase N (APN). Taken together with the non-competitive inhibition pattern, we also consider an alternative model of allosteric binding.


Assuntos
Aminopeptidases , Insulina , Animais , Insulina Regular Humana , Antígenos CD13 , Leucil Aminopeptidase , Piridinas
6.
PLoS One ; 19(3): e0300009, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451994

RESUMO

The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (ß = 0.765; se = 0.971; P = 0.430), while metformin treatment had a positive effect on heel BMD (ß = 1.414; se = 0.460; P = 2.118*10-3). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (ß = -0.526; se = 1.744; P = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (ß = 2.671; se = 1.340; P = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes.


Assuntos
Diabetes Mellitus , Gliclazida , Metformina , Humanos , Densidade Óssea/genética , Estudo de Associação Genômica Ampla , Gliclazida/farmacologia , Gliclazida/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina , Insulina Regular Humana , Análise da Randomização Mendeliana , Metformina/farmacologia , Metformina/uso terapêutico , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Rosiglitazona
7.
Commun Biol ; 7(1): 293, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459184

RESUMO

We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Glucose , Hemoglobinas Glicadas , Insulina/metabolismo , Insulina Regular Humana , Lipoproteínas , Análise da Randomização Mendeliana
8.
JAMA Netw Open ; 7(3): e243474, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38536176

RESUMO

Importance: The burden of diabetes is growing worldwide. The costs associated with diabetes put substantial pressure on patients and health budgets, especially in low- and middle-income countries. The prices of diabetes medicines are a key determinant for access, yet little is known about the association between manufacturing costs and current market prices. Objectives: To estimate the cost of manufacturing insulins, sodium-glucose cotransporter 2 inhibitors (SGLT2Is), and glucagonlike peptide 1 agonists (GLP1As), derive sustainable cost-based prices (CBPs), and compare these with current market prices. Design, Setting, and Participants: In this economic evaluation, the cost of manufacturing insulins, SGLT2Is, and GLP1As was modeled. Active pharmaceutical ingredient cost per unit (weighted least-squares regression model using data from a commercial database of trade shipments, data from January 1, 2016, to March 31, 2023) was combined with costs of formulation and other operating expenses, plus a profit margin with an allowance for tax, to estimate CBPs. Cost-based prices were compared with current prices in 13 countries, collected in January 2023 from public databases. Countries were selected to provide representation of different income levels and geographic regions based on the availability of public databases. Main Outcomes and Measures: Estimated CBPs; lowest current market prices (2023 US dollars). Results: In this economic evaluation of manufacturing costs, estimated CBPs for treatment with insulin in a reusable pen device could be as low as $96 (human insulin) or $111 (insulin analogues) per year for a basal-bolus regimen, $61 per year using twice-daily injections of mixed human insulin, and $50 (human insulin) or $72 (insulin analogues) per year for a once-daily basal insulin injection (for type 2 diabetes), including the cost of injection devices and needles. Cost-based prices ranged from $1.30 to $3.45 per month for SGLT2Is (except canagliflozin: $25.00-$46.79) and from $0.75 to $72.49 per month for GLP1As. These CBPs were substantially lower than current prices in the 13 countries surveyed. Conclusions and Relevance: High prices limit access to newer diabetes medicines in many countries. The findings of this study suggest that robust generic and biosimilar competition could reduce prices to more affordable levels and enable expansion of diabetes treatment globally.


Assuntos
Medicamentos Biossimilares , Diabetes Mellitus Tipo 2 , Humanos , Hipoglicemiantes , Insulina , Insulina Regular Humana
9.
Diabetes Obes Metab ; 26(5): 1950-1961, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38504142

RESUMO

AIM: To conduct a systematic review with meta-analysis to provide a comprehensive synthesis of randomized controlled trials (RCTs) and prospective cohort studies investigating the effects of currently available bolus advisors on glycaemic parameters in adults with diabetes. MATERIALS AND METHODS: An electronic search of PubMed, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov was conducted in December 2022. The risk of bias was assessed using the revised Cochrane Risk of Bias tool. (Standardized) mean difference (MD) was selected to determine the difference in continuous outcomes between the groups. A random-effects model meta-analysis and meta-regression were performed. This systematic review was registered on PROSPERO (CRD42022374588). RESULTS: A total of 18 RCTs involving 1645 adults (50% females) with a median glycated haemoglobin (HbA1c) concentration of 8.45% (7.95%-9.30%) were included. The majority of participants had type 1 diabetes (N = 1510, 92%) and were on multiple daily injections (N = 1173, 71%). Twelve of the 18 trials had low risk of bias. The meta-analysis of 10 studies with available data on HbA1c showed that the use of a bolus advisor modestly reduced HbA1c compared to standard treatment (MD -011%, 95% confidence interval -0.22 to -0.01; I2 = 0%). This effect was accompanied by small improvements in low blood glucose index and treatment satisfaction, but not with reductions in hypoglycaemic events or changes in other secondary outcomes. CONCLUSION: Use of a bolus advisor is associated with slightly better glucose control and treatment satisfaction in people with diabetes on intensive insulin treatment. Future studies should investigate whether personalizing bolus advisors using artificial intelligence technology can enhance these effects.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adulto , Feminino , Humanos , Masculino , Insulina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas , Hipoglicemiantes/uso terapêutico , Insulina Regular Humana
10.
Diabetes Technol Ther ; 26(4): 211-221, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38426909

RESUMO

Introduction: The Closing the Loop in Adults With Type 1 Diabetes (CLEAR) randomized crossover study compared a novel fully closed-loop insulin delivery system with no carbohydrate entry or mealtime bolusing (CamAPS HX), with standard insulin pump therapy and glucose sensor in adults with type 1 diabetes and suboptimal glycemic outcomes. This qualitative substudy aimed to understand the psychosocial impact of using the fully automated system. Materials and Methods: Adults participating in the CLEAR study were invited to take part in a virtual semistructured interview after they had completed 8 weeks using the fully closed-loop system. Recruitment continued until there was adequate representation and data saturation occurred. Interviews were anonymized and transcribed for in-depth thematic analysis using an inductive-deductive approach. Study participants were also asked to complete questionnaires assessing diabetes distress, hypoglycemia confidence, and closed-loop treatment satisfaction. Results: Eleven participants (eight male and three female; age range 26-66 years) were interviewed. After an initial adjustment period, interviewees reported enjoying a reduction in diabetes burden, freed-up mental capacity, and improved mood. All were happy with overnight glycemic outcomes, with the majority reporting benefits on sleep. Although experiences of postprandial glucose outcomes varied, all found mealtimes easier and less stressful, particularly when eating out. Negatives raised by participants predominantly related to the insulin pump hardware, but some also reported increased snacking and challenges around resuming carbohydrate counting at trial closeout. Conclusions: In adults with type 1 diabetes, use of a fully closed-loop insulin delivery system had significant quality-of-life benefits and provided a welcome break from the day-to-day demands of living with diabetes. Clinical Trial Registration: NCT04977908.


Assuntos
Diabetes Mellitus Tipo 1 , Insulina , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Insulina/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Glicemia , Hipoglicemiantes/uso terapêutico , Estudos Cross-Over , Resultado do Tratamento , Sistemas de Infusão de Insulina , Insulina Regular Humana/uso terapêutico
11.
Mol Pharm ; 21(4): 2025-2033, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38525800

RESUMO

Insulin aggregation poses a significant problem in pharmacology and medicine as it occurs during prolonged storage of the hormone and in vivo at insulin injection sites. We have recently shown that dominant forces driving the self-assembly of insulin fibrils are likely to arise from intermolecular interactions involving the N-terminal segment of the A-chain (ACC1-13). Here, we study how proline substitutions within the pilot GIVEQ sequence of this fragment affect its propensity to aggregate in both neutral and acidic environments. In a reasonable agreement with in silico prediction based on the Cordax algorithm, proline substitutions at positions 3, 4, and 5 turn out to be very effective in preventing aggregation according to thioflavin T-fluorescence-based kinetic assay, infrared spectroscopy, and atomic force microscopy (AFM). Since the valine and glutamate side chains within this segment are strongly involved in the interactions with the insulin receptor, we have focused on the possible implications of the Q → P substitution for insulin's stability and interactions with the receptor. To this end, comparative molecular dynamics (MD) simulations of the Q5P mutant and wild-type insulin were carried out for both free and receptor-bound (site 1) monomers. The results point to a mild destabilization of the mutant vis à vis the wild-type monomer, as well as partial preservation of key contacts in the complex between Q5P insulin and the receptor. We discuss the implications of these findings in the context of the design of aggregation-resistant insulin analogues retaining hormonal activity.


Assuntos
Amiloide , Insulina , Insulina/química , Prolina , Peptídeos , Insulina Regular Humana
12.
Probl Endokrinol (Mosk) ; 70(1): 91-99, 2024 Feb 28.
Artigo em Russo | MEDLINE | ID: mdl-38433545

RESUMO

The progressive nature of type 2 diabetes mellitus leads to the need for insulin therapy in a significant proportion of patients. Very often start of insulin therapy in type 2 diabetes mellitus (T2DM) is associated with weight gain and a significant increase of hypoglycemia's risk. However, innovative options, such as fixed ratio combinations of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulin, minimize weight gain and hypoglycemia risks and allow a greater proportion of patients to achieve individual glycemic control goals without compromising safety parameters. This review includes a description of the randomized clinical trials, as well as the results of real clinical practice of the use of two currently existing fixed ration combinations of GLP-1RA and basal insulin - iDegLira and iGlarLixi.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/uso terapêutico , Insulina Regular Humana , Hipoglicemia/induzido quimicamente , Aumento de Peso
13.
Diabetes Technol Ther ; 26(3): 190-197, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444313

RESUMO

Aim: To assess the real-world performance of MiniMed™ 780G for Australians with type 1 diabetes (T1D) following advanced hybrid closed loop (AHCL) activation and to evaluate the effect of changing from MiniMed 670/770G to 780G. Methods: We analyzed deidentified Carelink™ continuous glucose monitoring (CGM) data from Australian users from January 2020 to December 2022, including the proportion attaining three major consensus targets: Glucose management indicator (GMI <7.0%), time in range (TIR 70-180 mg/dL >70%), and time below range (TBR 70 mg/dL <4%). Results: Comparing 670/770G users (n = 5676) for mean ± standard deviation 364 ± 244 days with 780G users (n = 3566) for 146 ± 145 days, the latter achieved a higher TIR (72.6% ± 10.6% vs. 67.3% ± 11.4%; P < 0.001), lower time above range (TAR) (25.5% ± 10.9% vs. 30.6% ± 11.7%; P < 0.001), and lower GMI (6.9% ± 0.4% vs. 7.2% ± 0.4%; P < 0.001) without compromising TBR (1.9% ± 1.8% vs. 2.0% ± 1.8%; P = 0.0015). Of 1051 670/770G users transitioning to 780G, TIR increased (70.0% ± 10.7% to 74.0% ± 10.2%; P < 0.001), TAR decreased (28.1% ± 10.9% to 24.0% ± 10.7%; P < 0.001), and TBR was unchanged. The percentage of users attaining all three CGM targets was higher in 780G users (50.1% vs. 29.5%; P < 0.001). CGM metrics were stable at 12 months post-transition. Conclusion: Real-world data from Australia shows that a higher proportion of MiniMed 780G users meet clinical targets for CGM consensus metrics compared to MiniMed 670/770G users and glucose control was sustained over 12 months.


Assuntos
População Australasiana , Automonitorização da Glicemia , Insulina , Humanos , Austrália , Glicemia , Insulina/uso terapêutico , Insulina Regular Humana
14.
Diabetes Metab Res Rev ; 40(3): e3792, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38517704

RESUMO

AIMS: Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis. Furthermore, we examined islet pericytes for sulfatide, and beta-cell receptors for GLP-1, both of which are related to the insulin production. MATERIALS AND METHODS: We examined mRNA levels in islets from the DiViD and nPOD studies, performed genetic association analyses, and histologically investigated pericytes in the islets for sulfatide. RESULTS: Polymorphisms of the gene encoding the CERS6 enzyme responsible for synthesising dihydroceramide, a precursor to sulfatide, are associated with random blood glucose values in non-diabetic persons. This fits well with our finding of sulfatide in pericytes in the islets, which regulates the capillary blood flow in the islets of Langerhans, which is important for oxygen supply to insulin production. In the islets of newly diagnosed T1D patients, we observed low levels of GLP-1 receptors; this may explain the insulin resistance in their beta cells and their low insulin production. In T2D patients, we identified associated polymorphisms in both CERS2 and CERS6. CONCLUSIONS: Here, we describe several polymorphisms in sulfatide enzymes related to blood glucose levels and HbA1c in non-diabetic individuals. Islet pericytes from such persons contain sulfatide. Furthermore, low insulin secretion in newly diagnosed T1D may be explained by beta-cell insulin resistance due to low levels of GLP-1 receptors.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Ilhotas Pancreáticas , Humanos , Glicemia , Esfingolipídeos , Resistência à Insulina/genética , Pericitos , Sulfoglicoesfingolipídeos , Insulina , Insulina Regular Humana , Diabetes Mellitus Tipo 2/genética , Peptídeo 1 Semelhante ao Glucagon , Glucose
16.
PLoS One ; 19(3): e0300055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38442115

RESUMO

INTRODUCTION: Effective diabetes self-management and collaborative responsibility sharing with parents are imperative for pediatric patients with type 1 diabetes mellitus, particularly as they gradually assume more self-care responsibilities. The primary goal of this study was to assess differences in adherence to self-care activities regarding sociodemographics and clinical characteristics in pediatric patients with type 1 diabetes. The secondary goal of this study was to understand the level of parental involvement in diabetes management and to assess the pediatric patients' behaviors (independent or dependent on disease self-management) that relate to sociodemographic and clinical characteristics. METHODS: This was a comparative cross-sectional and correlational study. The study sample included 182 children and adolescents who had been diagnosed with type 1 diabetes at least 3 months prior. Data collection instruments included a sociodemographic and questionnaire about Adherence to self-care activities and parental involvement in diabetes self-management, as well as a documentation sheet for recording clinical data. RESULTS: A majority of participants (71%) exhibited non-adherence to self-care tasks, despite 78.0% asserting their independence in diabetes self-management. Notably, insufficient parental involvement in administering insulin therapy significantly predicted severe hypoglycemic episodes. CONCLUSIONS: Pediatric patients dealing with type 1 diabetes demonstrate a substantial degree of autonomy in managing their condition, paradoxically coupled with self-reported non-adherence to critical self-care responsibilities. Notably, children (aged 8-12) rely more heavily on parental support, especially concerning insulin therapy administration. The study underscores the crucial role of parental engagement in insulin therapy, as its deficiency significantly predicts the likelihood of severe hypoglycemic episodes.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Humanos , Criança , Autocuidado , Diabetes Mellitus Tipo 1/terapia , Estudos Transversais , Insulina Regular Humana , Insulina , Hipoglicemiantes
17.
Diabetes Technol Ther ; 26(3): 198-202, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444312

RESUMO

The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (n = 17) and without (n = 34) DKA at diagnosis. Participants with and without DKA at diagnosis had similar time in target glucose range 3.9-10.0 mmol/L (70-180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL) and HbA1c at 6, 12, and 24 months. While insulin requirements at 6 months were higher in those with DKA at diagnosis, this was not statistically significant after adjusting for bodyweight. Residual C-peptide secretion was similar between groups. We conclude that HCL therapy may mitigate against the negative glycemic effects of DKA at T1D diagnosis.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Adolescente , Humanos , Insulina/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/etiologia , Glicemia , Sistemas de Infusão de Insulina , Insulina Regular Humana
18.
Diabetes Technol Ther ; 26(3): 203-210, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444315

RESUMO

The growing use of continuous glucose monitoring (CGM) has been supported by expert consensus and clinical guidelines on glycemic management in diabetes with time in range (TIR 70-180 mg/dL) representing a key CGM-derived glucose metric. Time in tight range (TITR) has also been proposed for clinical use, spanning largely normal glucose levels of 70-140 mg/dL. However, keeping such narrow glucose ranges can be challenging, and understanding the factors modulating TITR can help achieve these tight glycemic targets. Our real-life study aimed to evaluate the relationship between average glucose (AG) and TIR/TITR in a large cohort (n = 22,006) of CGM users, divided into four groups: self-identified as having type 1 diabetes (T1D) treated with insulin using multiple daily injections (MDI) or pumps; type 2 diabetes (T2D) on MDI or insulin pumps; T2D on basal insulin only; and T2D not on insulin treatment. The T2D groups, regardless of treatment type, displayed the highest TIR and TITR values, associated with lowest glycemic variability measured as glucose coefficient of variation (CV; 23-30%). The T1D group showed the lowest TIR and TITR, associated with the highest CVs (36-38%). Overall, higher CV was associated with lower TIR and TITR for AG values below 180 and 140 mg/dL, respectively, with the reverse holding true for AG values above these thresholds. The discordance between AG and TIR/TITR was less pronounced in T2D compared with T1D, attributed to lower CV in the former group. It was also observed that TITR has advantages over TIR for assessing glycemia status and progress toward more stringent A1C, particularly when approaching normal glucose levels. The data detail how CV affects the AG relationship with TIR/TITR, which has implications for CGM interpretation. In many instances TITR, rather than TIR, may be preferable to employ once AG falls below 140 mg/dL and near-normal glucose levels are required clinically.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Automonitorização da Glicemia , Glicemia , Insulina Regular Humana , Glucose
19.
Diabetes Technol Ther ; 26(3): 184-189, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444317

RESUMO

Introduction: More than two-thirds of patients with type 1 diabetes (T1D) are overweight (OW) and/or obese (OB) in the USA and Western Europe, resulting in insulin resistance as in type 2 diabetes. None of the currently available glucagon like polypeptide 1 (GLP-1) analogs are approved for patients with T1D. A higher dose of semaglutide has been approved by the Food and Drug Administration (FDA) for subjects with body mass index (BMI) >27 kg/m2. We evaluated the real-world use of semaglutide in patients with T1D. Methods: This was a retrospective chart review study of 50 OW or OB patients with T1D who were initiated on semaglutide and followed for 1 year. The control group comprised of 50 computer-matched patients (for sex, race, weight, BMI, and diabetes duration) during a similar time period and were not on any weight loss medications. Results: Most patients (92%) were non-Hispanic white in both arms. Mean ± standard deviation (SD) age and duration of diabetes were 42 ± 11 and 27 ± 12 years, respectively. The continuous glucose monitors (CGM), insulin pump use, baseline BMI and body weight were also similar in the two groups. Baseline glycosylated hemoglobin (HbA1c) was insignificantly lower in the semaglutide group (7.6% vs. 8.2%, respectively; P = non-significant [NS]). Total daily insulin dose (TDD) and insulin dose per kg body weight were higher in the semaglutide group at baseline with no difference in basal or prandial insulin dose. There were significantly greater declines in mean (±SD), BMI (7.9% ± 2.6%), body weight (15.9 lbs ± 5.4 lbs), HbA1c, CGM glucose SD and coefficient of variation (CV), and increase in CGM time in range (TIR) in the semaglutide group compared to the control group with no difference in insulin dose changes, time above range (TAR), or time below range (TBR). Conclusions: We conclude that use of semaglutide in patients who are OW and/or OB with T1D was effective in lowering body weight and BMI, and improving glycemic metrics in this pilot real-world study. We strongly recommend performing prospective, large-randomized clinical trials with newer GLP-1 analogs like semaglutide and tirzepatide (twin-cretin) for subjects with T1D associated with OW and/or OB.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Estados Unidos , Humanos , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Estudos Prospectivos , Estudos Retrospectivos , Obesidade/complicações , Obesidade/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Insulina Regular Humana , Insulina , Glucose
20.
Diabetes Technol Ther ; 26(3): 156-160, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444314

RESUMO

Aim: The impact of weight gain on insulin dosage and glycemic control in adults with type 1 diabetes (T1D) aged 25 years and older was investigated in the T1D Exchange Registry participants. Methods: Participants were categorized into four groups based on their change in weight from T1D Exchange registry enrollment to year 5: stable weight (-5 to <5 lb), gained 5 to <10 lb, gained 10 to <20 lb, or gained ≥20 lb. Those who lost >5 lb were excluded. The primary outcomes were glucose control, as measured by glycosylated hemoglobin (HbA1c), and total daily insulin dose (TDD) at year 5. Linear regression models were used to evaluate the association between weight gain, HbA1c, and TDD. Results: There were 1969 participants included in the analyses. The mean ± standard deviation age was 45 ± 13 years, 57% were female, and 92% were White non-Hispanic. For those with an enrollment HbA1c <8.0%, the mean HbA1c at year 5 was higher for those who gained ≥20 lb compared to those with a stable weight of -5 to <5 lb (7.4% ± 1.1% vs. 7.2% ± 0.8%, respectively; P = 0.005). For this cohort, the mean TDD at year 5 increased from 49 ± 25 to 61 ± 29 U for those who gained ≥20 lb, while decreased from 45 ± 27 to 44 ± 25 U for those with stable weight of -5 to <5 lb (P < 0.001). Among participants with an enrollment HbA1c ≥9.0%, the mean HbA1c at year 5 was statistically insignificant at 8.4% ± 1.3% for those who gained ≥20 lb compared to 9.2% ± 1.7% for those with a stable weight of -5 to <5 lb (P = 0.09). Conclusion: Significant weight gain in adults with T1D who had good to adequate glycemic control was associated with modest deterioration in glucose control despite an increase in TDD. Worsening glucose control may indicate insulin resistance related to weight gain despite significantly increased insulin dosage which was insufficient to maintain adequate glycemic control.


Assuntos
Diabetes Mellitus Tipo 1 , Adulto , Feminino , Humanos , Masculino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicemia , Hemoglobinas Glicadas , Controle Glicêmico , Sistema de Registros , Insulina Regular Humana , Insulina/uso terapêutico , Aumento de Peso
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