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1.
J Assoc Physicians India ; 69(8): 11-12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34472814

RESUMO

Around 300- 400 AD, ancient Indian physicians described a condition akin to diabetes mellitus which was called "Madhumeha". Sushrutha and Charaka, are also credited with describing two types of diabetes which would roughly correspond to type 1 diabetes and type 2 diabetes. However, little is known about the history of diabetes in India between the first and 19th century AD. A thorough search of literature revealed a large number of publications on diabetes from India in the 1800s and early 1900s, mostly from Calcutta and the Madras Presidency, suggesting that the prevalence of diabetes was high in these two places. Building on the observations made by a number of English physicians, Chunilal Bose in 1907 suggested the link between diabetes and lifestyle in India. Amazingly, India did not have to wait long after the discovery of insulin by Banting and Best at Toronto in 1921, to get its own supply. Around this time, Dr. J.P. Bose, eminent physician and diabetologist from Calcutta made remarkable contributions to the study of diabetes in India. He was also the first to describe the dramatic effects of insulin administration to children with type 1 diabetes in India. All these facts have remained largely forgotten which prompted the authors to delve deep into the history of diabetes in pre-independence India. This has led to the unearthing of several pearls of knowledge which are presented in this article as a fitting tribute to the 100th year of Insulin Discovery.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Médicos , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , História do Século XX , Humanos , Índia/epidemiologia , Insulina , Masculino
2.
Rev Med Chil ; 149(3): 330-338, 2021 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-34479311

RESUMO

BACKGROUND: Previous studies have assessed the role of Type 1 diabetes (DM1) antibodies as predictors of the natural history of disease. AIM: To determine the frequency and combinations of positivity for DM1 antibodies in patients with DM1 and the relationship between antibody positivity and the age of the patient. To explore the relationship between history of insulin therapy or diabetic ketoacidosis (DKA) at the onset of the disease with antibody positivity in a subsample. MATERIAL AND METHODS: Data was gathered from every sample processed for DM1 antibodies in our laboratory between January 2015 and September 2019. Medical records from 84 patients who tested positive for at least one antibody were revised to study the relationship between insulin therapy or DKA at the onset of the disease with antibody positivity. RESULTS: Forty percent of DM1 antibody tests were positive. Among positive tests, 1, 2, 3 or 4 DM1 antibodies were detected in 48%, 33%, 17% and 3% of cases, respectively. The likelihood of testing positive was inversely related with age for ICA, GAD, IA-2, ZnT8 and directlyproportionalforIAA (p= -0,012; -0,013; -0,014; -0,009; 0,005 respectively). An association between DKA at the onset of the disease and IA-2 positivity was observed (Odds ratio (OR) 5.38 95% confidence intervals (CI) 1.79 - 16.16, P < 0.01). No association was found between IAA positivity and history of insulin therapy (OR 2.25 95%CI 0.63 - 7.90, P = 0.2403). The results obtained from this study represent a novel local profile of DM1 antibody data, highlighting a relationship between antibody positivity and age.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Autoanticorpos , Chile/epidemiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Cetoacidose Diabética/epidemiologia , Humanos , Insulina/uso terapêutico
3.
Sensors (Basel) ; 21(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34372462

RESUMO

Technology advances have made possible improvements such as Continuous Glucose Monitors, giving the patient a glucose reading every few minutes, or insulin pumps, allowing more personalized therapies. With the increasing number of available closed-loop systems, new challenges appear regarding algorithms and functionalities. Several of the analysed systems in this paper try to adapt to changes in some patients' conditions and, in several of these systems, other variables such as basal needs are considered fixed from day to day to simplify the control problem. Therefore, these systems require a correct adjustment of the basal needs profile which becomes crucial to obtain good results. In this paper a novel approach tries to dynamically determine the insulin basal needs of the patient and use this information within a closed-loop algorithm, allowing the system to dynamically adjust in situations of illness, exercise, high-fat-content meals or even partially blocked infusion sites and avoiding the need for setting a basal profile that approximately matches the basal needs of the patient. The insulin sensitivity factor and the glycemic target are also dynamically modified according to the situation of the patient. Basal insulin needs are dynamically determined through linear regression via the decomposition of previously dosed insulin and its effect on the patient's glycemia. Using the obtained value as basal insulin needs and other mechanisms such as basal needs modification through its trend, ISF and glycemic targets modification and low-glucose-suspend threshold, the safety of the algorithm is improved. The dynamic basal insulin needs determination was successfully included in a closed-loop control algorithm and was simulated on 30 virtual patients (10 adults, 10 adolescent and 10 children) using an open-source python implementation of the FDA-approved (Food and Drug Administration) UVa (University of Virginia)/Padova Simulator. Simulations showed that the proposed system dynamically determines the basal needs and can adapt to a partial blockage of the insulin infusion, obtaining similar results in terms of time in range to the case in which no blockage was simulated. The proposed algorithm can be incorporated to other current closed-loop control algorithms to directly estimate the patient's basal insulin needs or as a monitoring channel to detect situations in which basal needs may differ from the expected ones.


Assuntos
Diabetes Mellitus Tipo 1 , Pâncreas Artificial , Adolescente , Adulto , Algoritmos , Glicemia , Automonitorização da Glicemia , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes , Insulina , Sistemas de Infusão de Insulina
4.
Medicine (Baltimore) ; 100(29): e26743, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398053

RESUMO

ABSTRACT: The aim of this study was to explore the values of ultrasound for diagnosis and management of insulin-induced lipohypertrophy and further analyzing the impact of body mass index and subcutaneous fat thickness on ultrasound manifestations of lipohypertrophy.In this 3-month, prospective cohort study, a total of 162 patients with diabetes who used insulin therapy more than 1 year with unknown lipohypertrophy status were enrolled into this study. Demographic information, assessment of glycemic control and insulin injection technique were evaluated. Physical and ultrasound examination were separately performed to detect lipohypertrophy by a team of diabetes educator nurses or ultrasonographer in a blinded fashion. Patients with lipohypertrophy received insulin injection technique education based on ultrasound examination and Chinese guideline.Ultrasound examination detected 41.1% more patients (74.1% vs 52.5%; P < .001) with lipohypertrophy and 61.2% more lesions (216 vs 134; P < .001) than physical examination. Glycosylated hemoglobin A1c and fasting blood glucose were significantly decreased in patients with lipohypertrophy or subclinical lipohypertrophy (lipohypertrophy without visual and palpation changes) after receiving insulin injection technique education based on ultrasound examination and Chinese guideline than baseline at 3 months (P < .001). The proportion of lesions with ultrasound manifestation 2 (distortion of surrounding connective tissue) in obese and STF (>15 mm) groups were no more than 50% and showed a decreased trend with increased subcutaneous fat thickness and body mass index (P < .001).Lipohypertrophy has characteristic ultrasound manifestations which can detect more accurate results than palpation alone and provide detailed information to promote effective education on lipohypertrophy management, thereby improving glycemic control.


Assuntos
Lipodistrofia/diagnóstico , Glicemia , China , Estudos de Coortes , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobina A Glicada , Humanos , Insulina/efeitos adversos , Lipodistrofia/induzido quimicamente , Lipodistrofia/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Ultrassonografia
5.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371877

RESUMO

Pathological mechanisms underlining diabetic bone defects include oxidative damage and insulin/IGF-1 imbalance. Morin is a bioflavonoid with antioxidant and anti-diabetic effects. This study evaluates morin's protective effects against altered bone histomorphometry in diabetic rats through assessing insulin/IGF-1 pathway as a potential mechanism. Diabetic animals were administered two morin doses (15 and 30 mg/kg) for 5 weeks. Different serum hepatic and renal functions tests were assessed. Bone density and histomorphometry in cortical and trabecular tissues were evaluated histologically. The expressions of insulin, c-peptide and IGF-1 were estimated. In addition, the enzymatic activities of the major antioxidant enzymes were determined. Diabetic-associated alterations in serum glucose, aminotransferases, urea and creatinine were attenuated by morin. Diabetic bone cortical and trabecular histomorphometry were impaired with increased fibrosis, osteoclastic functions, osteoid formation and reduced mineralization, which was reversed by morin; particularly the 30 mg/kg dose. Insulin/IGF-1 levels were diminished in diabetic animals, while morin treatment enhanced their levels significantly. Diabetes also triggered systemic oxidative stress noticeably. The higher dose (30 mg/kg) of morin corrected the endogenous antioxidant enzymatic activities in diabetic rats. Findings indicate the potential value of morin supplementation against hyperglycemia-induced skeletal impairments. Activation of insulin/IGF-1 signaling could be the underlining mechanism behind these effects.


Assuntos
Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Fêmur/efeitos dos fármacos , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Insulina/sangue , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/patologia , Fêmur/metabolismo , Fêmur/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais , Estreptozocina
6.
Lancet Diabetes Endocrinol ; 9(8): 502-514, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34214479

RESUMO

BACKGROUND: Type 1 diabetes results from autoimmune-mediated destruction of ß cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving ß-cell function in patients with recent-onset type 1 diabetes. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients with recent-onset type 1 diabetes (<100 days from diagnosis), aged 18-45 years, positive for at least one type of diabetes-associated autoantibody, and with a peak stimulated C-peptide of greater than 0·2 nmol L-1 on a mixed meal tolerance test (MMTT) were enrolled from nine medical centres in the USA (n=8) and Australia (n=1). Participants were randomly assigned (2:1) to receive either 400 mg imatinib mesylate (4 × 100 mg film-coated tablets per day) or matching placebo for 26 weeks via a computer-generated blocked randomisation scheme stratified by centre. Treatment assignments were masked for all participants and study personnel except pharmacists at each clinical site. The primary endpoint was the difference in the area under the curve (AUC) mean for C-peptide response in the first 2 h of an MMTT at 12 months in the imatinib group versus the placebo group, with use of an ANCOVA model adjusting for sex, baseline age, and baseline C-peptide, with further observation up to 24 months. The primary analysis was by intention to treat (ITT). Safety was assessed in all randomly assigned participants. This study is registered with ClinicalTrials.gov, NCT01781975 (completed). FINDINGS: Patients were screened and enrolled between Feb 12, 2014, and May 19, 2016. 45 patients were assigned to receive imatinib and 22 to receive placebo. After withdrawals, 43 participants in the imatinib group and 21 in the placebo group were included in the primary ITT analysis at 12 months. The study met its primary endpoint: the adjusted mean difference in 2-h C-peptide AUC at 12 months for imatinib versus placebo treatment was 0·095 (90% CI -0·003 to 0·191; p=0·048, one-tailed test). This effect was not sustained out to 24 months. During the 24-month follow-up, 32 (71%) of 45 participants who received imatinib had a grade 2 severity or worse adverse event, compared with 13 (59%) of 22 participants who received placebo. The most common adverse events (grade 2 severity or worse) that differed between the groups were gastrointestinal issues (six [13%] participants in the imatinib group, primarily nausea, and none in the placebo group) and additional laboratory investigations (ten [22%] participants in the imatinib group and two [9%] in the placebo group). Per the trial protocol, 17 (38%) participants in the imatinib group required a temporary modification in drug dosing and six (13%) permanently discontinued imatinib due to adverse events; five (23%) participants in the placebo group had temporary modifications in dosing and none had a permanent discontinuation due to adverse events. INTERPRETATION: A 26-week course of imatinib preserved ß-cell function at 12 months in adults with recent-onset type 1 diabetes. Imatinib might offer a novel means to alter the course of type 1 diabetes. Future considerations are defining ideal dose and duration of therapy, safety and efficacy in children, combination use with a complimentary drug, and ability of imatinib to delay or prevent progression to diabetes in an at-risk population; however, careful monitoring for possible toxicities is required. FUNDING: Juvenile Research Diabetes Foundation.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 1/patologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
7.
BMJ Open ; 11(7): e050713, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261691

RESUMO

INTRODUCTION: Optimising glycaemic control in type 1 diabetes (T1D) remains challenging. Flash glucose monitoring with FreeStyle Libre 2 (FSL2) is a novel alternative to the current standard of care self-monitoring of blood glucose (SMBG). No randomised controlled trials to date have explored the potential benefits of FSL2 in T1D. We aim to assess the impact of FSL2 in people with suboptimal glycaemic control T1D in comparison with SMBG. METHODS: This open-label, multicentre, randomised (via stochastic minimisation), parallel design study conducted at eight UK secondary and primary care centres will aim to recruit 180 people age ≥16 years with T1D for >1 year and glycated haemoglobin (HbA1c) 7.5%-11%. Eligible participants will be randomised to 24 weeks of FSL2 (intervention) or SMBG (control) periods, after 2-week of blinded sensor wear. Participants will be assessed virtually or in-person owing to the COVID-19 pandemic. HbA1c will be measured at baseline, 12 and 24 weeks (primary outcome). Participants will be contacted at 4 and 12 weeks for glucose optimisation. Control participants will wear a blinded sensor during the last 2 weeks. Psychosocial outcomes will be measured at baseline and 24 weeks. Secondary outcomes include sensor-based metrics, insulin doses, adverse events and self-report psychosocial measures. Utility, acceptability, expectations and experience of using FSL2 will be explored. Data on health service resource utilisation will be collected. ANALYSIS: Efficacy analyses will follow intention-to-treat principle. Outcomes will be analysed using analysis of covariance, adjusted for the baseline value of the corresponding outcome, minimisation factors and other known prognostic factors. Both within-trial and life-time economic evaluations, informed by modelling from the perspective of the National Health Service setting, will be performed. ETHICS: The study was approved by Greater Manchester West Research Ethics Committee (reference 19/NW/0081). Informed consent will be sought from all participants. TRIAL REGISTRATION NUMBER: NCT03815006. PROTOCOL VERSION: 4.0 dated 29 June 2020.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Adolescente , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes , Estudos Multicêntricos como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Medicina Estatal , Reino Unido
8.
Gene ; 799: 145847, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34274473

RESUMO

BACKGROUND: Uncontrolled type 1 diabetes mellitus (T1D) impairs reproductive potential of males. Insulin treatment restores metabolic parameters but it is unclear how it protects male reproductive health. Herein, we hypothesized that insulin treatment to T1D rats protects testicular physiology by mediating mechanisms associated with apoptosis and cell cycle. METHODS: Mature male Wistar rats (n = 24) were divided into 3 groups: control, T1D-induced (received 40 mg kg-1 streptozotocin) and insulin-treated T1D (Ins T1D; received 40 mg kg-1 streptozotocin and then treated 0.9 IU/100 gr of insulin for 56 days) (N = 8/group). Expression levels of intrinsic apoptosis pathways regulators (Bcl-2, Bax, Caspase-3 and p53) and core regulators of cell cycle machinery (Cyclin D1, Cdk-4 and p21) were determined in testicular tissue by immunohistochemistry (IHC) and RT-PCR techniques. The percentage of testicular apoptotic cells was evaluated by TUNEL staining. RESULTS: Our data shows that insulin treatment to T1D rats restored (P < 0.05) T1D-induced increased of caspase-3 and p53 expression in testis. Moreover, the testis of T1D rats treated with insulin exhibited increased expression of Cyclin D1 and cdk-4, and a reduced expression of p21 when compared with the expression in testis of T1D rats. Finally, insulin treatment could fairly control T1D-induced apoptosis. Accordingly, treatment of T1D rats with insulin led to a remarkable reduction (p < 0.05) in the percentage of apoptotic cells in the testis. CONCLUSIONS: Insulin treatment is able to restore the network expression of apoptosis and proliferation-related genes caused by T1D in the testis and via this mechanism, preserve the fertility of males.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/fisiologia , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Fertilidade , Expressão Gênica/efeitos dos fármacos , Masculino , Substâncias Protetoras/farmacologia , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue
9.
Science ; 373(6554): 522-527, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34326234

RESUMO

Despite innovations in insulin therapy since its discovery, most patients living with type 1 diabetes do not achieve sufficient glycemic control to prevent complications, and they experience hypoglycemia, weight gain, and major self-care burden. Promising pharmacological advances in insulin therapy include the refinement of extremely rapid insulin analogs, alternate insulin-delivery routes, liver-selective insulins, add-on drugs that enhance insulin effect, and glucose-responsive insulin molecules. The greatest future impact will come from combining these pharmacological solutions with existing automated insulin delivery methods that integrate insulin pumps and glucose sensors. These systems will use algorithms enhanced by machine learning, supplemented by technologies that include activity monitors and sensors for other key metabolites such as ketones. The future challenges facing clinicians and researchers will be those of access and broad clinical implementation.


Assuntos
Automonitorização da Glicemia , Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico , Hipoglicemiantes/uso terapêutico , Insulinas/uso terapêutico , Absorção Fisiológica , Algoritmos , Automação , Diabetes Mellitus Tipo 1/sangue , Humanos , Sistemas de Infusão de Insulina , Insulinas/administração & dosagem , Insulinas/sangue , Insulinas/farmacocinética , Refeições
10.
Anticancer Res ; 41(8): 4053-4059, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281874

RESUMO

BACKGROUND/AIM: Diabetes is a risk factor for dementia. However, no radical preventive method for diabetes-associated dementia has yet been developed. Our previous study revealed that oral administration of lipopolysaccharide (LPS) prevents high-fat diet-induced cognitive impairment. Therefore, we investigated here whether oral administration of LPS (OAL) could also prevent diabetes-associated dementia. MATERIALS AND METHODS: Diabetic mice were produced by intraperitoneal administration of streptozotocin (STZ), and then mice were orally administered LPS. Cognitive ability was evaluated using the Morris water maze, and gene expression was analyzed in isolated microglia. RESULTS: OAL prevented STZ-induced diabetic cognitive impairment, but did not affect blood glucose levels. Moreover, OAL promoted the expression of neuroprotective genes in microglia, such as heat shock protein family 40 (HSP40) and chemokine CCL7. CONCLUSION: OAL prevents diabetes-associated dementia, potentially via promotion of HSP40 and CCL7 expression in microglia.


Assuntos
Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Administração Oral , Animais , Glicemia/efeitos dos fármacos , Quimiocina CCL7/genética , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/genética , Proteínas de Choque Térmico HSP40/genética , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia
11.
Medicine (Baltimore) ; 100(27): e26417, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232173

RESUMO

BACKGROUND: Currently, there are a number of sodium glucose co-transport-2 (SGLT2) inhibitors that are under development or in clinical trials. Prior meta-analyses had established the safety and efficacy of SGLT2 inhibitors in type 1 diabetes mellitus (T1DM), but with low level of evidences and inconsistent conclusions. However, recently many new randomized clinical trials (RCTs) have been published, we hence try to design a study protocol to assess the effect of SGLT2 inhibitors on cardiovascular events via a comprehensive meta-analysis of data from much more RCTs, including sensitivity and subgroup analyses. METHODS: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines to conduct this meta-analysis. Two investigators will perform a systematic search of scientific literature in the databases (from conception through June 12, 2021), including PubMed, Embase, and Cochrane Central Register of Controlled Trials. This meta-analysis will be conducted using RevMan statistical software. The risk of bias for each included study will be assessed using the Cochrane Risk of Bias Assessment Tool. RESULTS: Our protocol is conceived to test the hypothesis that SGLT2 inhibitors could lead to better outcomes in patients presenting with T1DM. REGISTRATION NUMBER: 10.17605/OSF.IO/ZD8WX.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Controle Glicêmico , Humanos
13.
Endocrinol Diabetes Metab ; 4(3): e00228, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34268452

RESUMO

Introduction: Severe COVID-19 has been anecdotally associated with high insulin requirements. It has been proposed that this may be driven by a direct diabetogenic effect of the virus that is unique to SARS-CoV-2, but evidence to support this is limited. To explore this, we compared insulin requirements in patients with severe COVID-19 and non-COVID-19 viral pneumonitis. Methods: This is a retrospective cohort study of patients with severe COVID-19 admitted to our intensive care unit between March and June 2020. A historical control cohort of non-COVID-19 viral pneumonitis patients was identified from routinely collected audit data. Results: Insulin requirements were similar in patients with COVID-19 and non-COVID-19 viral pneumonitis after adjustment for pre-existing diabetes and severity of respiratory failure. Conclusions: In this single-centre study, we could not find evidence of a unique diabetogenic effect of COVID-19. We suggest that high insulin requirements in this disease relate to its propensity to cause severe respiratory failure in patients with pre-existing metabolic disease.


Assuntos
COVID-19/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insuficiência Respiratória/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino
15.
Nat Genet ; 53(7): 962-971, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34127860

RESUMO

We report the largest and most diverse genetic study of type 1 diabetes (T1D) to date (61,427 participants), yielding 78 genome-wide-significant (P < 5 × 10-8) regions, including 36 that are new. We define credible sets of T1D-associated variants and show that they are enriched in immune-cell accessible chromatin, particularly CD4+ effector T cells. Using chromatin-accessibility profiling of CD4+ T cells from 115 individuals, we map chromatin-accessibility quantitative trait loci and identify five regions where T1D risk variants co-localize with chromatin-accessibility quantitative trait loci. We highlight rs72928038 in BACH2 as a candidate causal T1D variant leading to decreased enhancer accessibility and BACH2 expression in T cells. Finally, we prioritize potential drug targets by integrating genetic evidence, functional genomic maps and immune protein-protein interactions, identifying 12 genes implicated in T1D that have been targeted in clinical trials for autoimmune diseases. These findings provide an expanded genomic landscape for T1D.


Assuntos
Alelos , Mapeamento Cromossômico , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Variação Genética , Genômica , Autoimunidade/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Descoberta de Drogas , Expressão Gênica , Genômica/métodos , Humanos , Terapia de Alvo Molecular , Mapeamento de Interação de Proteínas
16.
Adv Ther ; 38(7): 3924-3936, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34091874

RESUMO

INTRODUCTION: Our aim was to evaluate the effects of 36 months of treatment with citicoline and vitamin B12 eye drops on macular function in patients with type 1 diabetes (DM1) with mild signs of non-proliferative diabetic retinopathy (NPDR). METHODS: A prospective, randomized, interventional, monocentric, double-masked study was conducted. Twenty patients with DM1 were enrolled and randomly divided into two groups: the DC group (10 patients; mean age ± standard deviation 46.86 ± 8.78 years) in which one eye of each patient was treated with citicoline and vitamin B12 eye drops (OMK2®, Omikron Italia srl, Italy, one drop thrice daily) for a period of 36 months; the DP group (10 patients; mean age ± standard deviation 47.89 ± 7.74 years) in which one eye of each patient was treated with placebo (eye drops containing hypromellose 0.3%, one drop thrice daily) for a period of 36 months. A total of 18 eyes (10 from the DP and 8 from the DC group, respectively) completed the study. In both groups, multifocal electroretinogram (mfERG) recordings were assessed at baseline and after 36 months. In mfERG analysis, the N1-P1 response amplitude density (RAD) evaluated in the 0-2.5° (ring 1), in the 2.5-5° (ring 2), in the 5-10° (ring 3), and in the 0-10° (ring 1 + ring 2 + ring 3) were considered. RESULTS: With respect to baseline, after 36 months of follow-up, the mfERG RADs recorded in R1, R2, R3, and R1 + R2 + R3 were significantly increased (i.e., R1 + R2 + R3 RAD from 21.552 ± 2.522 nV/degree2 at baseline to 26.912 ± 2.850 nV/degree2 at 36 months) in DC eyes, whereas in DP eyes they were significantly reduced (i.e., R1 + R2 + R3 RAD from 21.033 ± 3.574 nV/degree2 at baseline to 16.151 ± 3.571 nV/degree2 at 36 months). CONCLUSIONS: This study indicates that patients with NPDR treated with citicoline and vitamin B12 eye drops for a 36-month period achieved an improvement of the macular bioelectrical responses detectable by mfERG recordings. By contrast, during the same period of follow-up, patients with NPDR treated with placebo showed a worsening of the macular function.


Assuntos
Diabetes Mellitus Tipo 1 , Retinopatia Diabética , Citidina Difosfato Colina/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Humanos , Itália , Soluções Oftálmicas , Projetos Piloto , Estudos Prospectivos , Retina , Vitamina B 12 , Vitaminas
17.
Diabetes Obes Metab ; 23(8): 1936-1941, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34180122

RESUMO

AIM: To evaluate two methods of transition from an insulin pump to multiple daily injections (MDI) using long-acting insulin degludec (IDeg). MATERIALS AND METHODS: After a 1-week run-in period, adults with type 1 diabetes for longer than 1 year and HbA1c 48-69 mmol/mol (6.5%-8.5%), who had been using an insulin pump at least for 6 months, were randomly transitioned to either standard of care (discontinued insulin pump and started IDeg in 1:1 dose) or overlap (IDeg 1:1 at pump basal dose, but pump continued for the first 48 hours with a gradual basal reduction; 50% from 0-24 hours, 75% from 24-48 hours and then pump discontinued). Participants used blinded Dexcom G6 and the IDeg dose was not changed during the trial. Primary (% time above 180 mg/dL) and secondary (% time in 70-180 mg/dL and below 70 mg/dL) outcomes were compared between the two groups during 7 days of randomization. RESULTS: Age, gender, diabetes duration and basal/bolus insulin doses were similar between patients randomized to standard of care (n = 17) or overlap (n = 13) transition. Compared with overlap transition, the standard of care group spent 4.8% more time in hyperglycaemia (least square mean 4.8% [95% CI -3.3%, 12.9%]) and 5.3% less time in range (-5.3% [-12.6%, -2.0%]), without a significant difference in hypoglycaemia (0.5% [-2.3%,3.4%]). No treatment-related adverse events were noted in either group. CONCLUSION: The overlap transition method may result in a significant improvement in time-in-range without increasing hypoglycaemia during the first week of transition from an insulin pump to MDI using IDeg in adults with type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Adulto , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Insulina de Ação Prolongada/uso terapêutico
18.
Clin Drug Investig ; 41(7): 615-627, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34110613

RESUMO

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors have greatly improved cancer treatment. However, they are associated with immune-related adverse events, including autoimmune diseases (ADs) owing to their immune enhancement effect. As there are few comprehensive studies of ADs by ICIs, it is necessary to analyze the period information of drug-induced ADs. We also assumed that the temporal information may be useful to estimate the similarity of the pathogenic mechanism between spontaneous and ICI-induced ADs. METHODS: A period analysis including the Weibull analysis was performed on ICI-induced ADs using the Japanese Adverse Drug Event Report (JADER) database. For evaluating the similarity of spontaneous and ICI-induced ADs, a hierarchical cluster analysis was conducted to compare the different onset-time ranges. RESULTS: Type 1 diabetes mellitus, autoimmune colitis, and pemphigoid occurred earlier with CTLA-4 inhibitors (median: 46, 29.5 and 28 days, respectively) than with PD-1 inhibitors (> 130 days). Myasthenia gravis had a median time to onset of approximately 1 month, and the risk of onset would increase over time in ipilimumab combination therapy. This result reveals ADs that require attention. Using cluster analysis, we estimated six clusters with different patterns of onset times. Based on these results and a detailed previous research survey, the possible pathogenesis of drug-induced ADs was also discussed. CONCLUSIONS: This paper describes risk profiles with temporal information of ICI-induced ADs and proposes certain indicators for deciphering the mechanism of AD onset.


Assuntos
Doenças Autoimunes/diagnóstico , Inibidores de Checkpoint Imunológico/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/metabolismo , Análise por Conglomerados , Bases de Dados Factuais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Japão , Miastenia Gravis/tratamento farmacológico , Razão de Chances , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo
19.
Vasc Health Risk Manag ; 17: 259-266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079273

RESUMO

Background: It is expected that around 50% of individuals with diabetes mellitus will develop hypertension in the course of medical follow-up. However, with strict medical follow-up and adherence to medical advice the incidence of hypertension can be highly reduced and the time to occurrence can be delayed. Therefore, this paper aimed to measure the time to development of hypertension and identify its predictors among a 10-year cohort of diabetic patients who have medical follow-up in health facilities of Gurage Zone. Methods: An institution-based retrospective cohort study was conducted in diabetic follow-up clinics of Gurage Zone by reviewing 540 consecutively selected records among the records enrolled from January 1, 2010 to December 31, 2019. The outcome variable was incidence rate and survival time to the occurrences of hypertension (a systolic blood pressure at or above 140 mmHg and/or a diastolic blood pressure at or above 90 mm Hg and known hypertensive cases taken from adults' age ≥18 years) among admitted diabetic patients (fasting blood sugar ≥126 mg/dL or random blood sugar ≥200 mg/dL). Data were collected using a standardized checklist by trained professionals by reviewing records of all clients ever enrolled. Data were cleaned and entered by Epi info version 7 and analyzed by STATA. A Cox-proportional hazard regression model was built to identify predictors of development of hypertension. Results: A total of 540 clients were followed for different periods with a median follow-up period of 2.3 years which gives 3,200 person-years of observation. Two hundred and seventy-six (51.1%) participants were males and the mean age of was 52.2 (+11.7) years. Three hundred (55.6%) participants were urban dwellers. The overall incidence density rate (IDR) of hypertension in the cohort was 48.6 cases per 1,000 persons-year. Older ages adjusted hazard ratio (AHR)=4.0 (95% CI=2.26-7.82), body mass index (BMI) >25 kg/m2 AHR=2.3 (95% CI=1.06-3.68), Type II diabetes mellitus (DM) AHR=2.0 (95% CI=1.16-3.04), presence of comorbidity AHR=2.9 (95% CI=1.74-4.58), and poor drug adherence AHR=2.5 (95% CI=1.45-4.65) predicted the development of hypertension. Conclusion: The risk of occurrences of hypertension among diabetic patients was high at the early periods and the risk was less at the late diabetic periods and the incidence density rate of hypertension among diabetic patients was high. In addition, age, BMI, type of DM, comorbidity, and drug adherence were independent predictors of occurrences of hypertension. Therefore, intervention to further reduce its occurrence has to focus on drug adherence and prevention of infection.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Adulto , Fatores Etários , Índice de Massa Corporal , Comorbidade , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Etiópia/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/prevenção & controle , Hipoglicemiantes/uso terapêutico , Incidência , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
20.
Metabolism ; 121: 154814, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119537

RESUMO

Diabetes, one of the most prevalent chronic diseases in the world, is strongly associated with a poor prognosis in COVID-19. Scrupulous blood sugar management is crucial, since the worse outcomes are closely associated with higher blood sugar levels in COVID-19 infection. Although recent observational studies showed that insulin was associated with mortality, it should not deter insulin use in hospitalized patients requiring tight glucose control. Back and forth dilemma in the past with regards to continue/discontinue certain medications used in diabetes have been mostly resolved. The initial fears of consequences related to continuing certain medications have been largely dispelled. COVID-19 also necessitates the transformation in diabetes care through the integration of technologies. Recent advances in health-related technologies, notably telemedicine and remote continuous glucose monitoring, have become essential in the management of diabetes during the pandemic. Today, these technologies have changed the landscape of medicine and become more important than ever. Being a high-risk population, patients with type 1 or type 2 diabetes, should be prioritized for vaccination. In the future, as the pandemic fades, the prevalence of non-communicable diseases is expected to rise due to lifestyle changes and medical issues/dilemma encountered during the pandemic.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Glicemia/metabolismo , Automonitorização da Glicemia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suscetibilidade a Doenças , Humanos , Hipoglicemiantes/uso terapêutico , Pandemias , SARS-CoV-2/isolamento & purificação
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