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1.
Br J Community Nurs ; 26(11): 544-552, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731035

RESUMO

Type 1 diabetes is a lifelong condition which affects all age ranges, for reasons unknown, and the UK has one of the highest incidences of this complex condition in the world. Type 1 diabetes is caused by autoimmune damage to the insulin-producing ß-cells found in the pancreatic islet cells, leading to severe insulin deficiency. People with diabetes need to achieve a target glyosylated haemoglobin level to avoid macro- and microvascular complications, but there is the associated risk of hypoglycaemic events. These can vary in severity and consequences but will likely always cause worry for the person living with diabetes. There are many risk factors and reasons to be explored when looking at hypoglycaemia. This case study explores the nursing interventions that can be safely worked through and prioritised, within the community setting, to allow people with diabetes to be safe from severe hypoglycaemia, thus improving their quality of life and safety, as well as reducing costs for the NHS.


Assuntos
Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 1/enfermagem , Hemoglobina A Glicada/análise , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemia/etiologia , Hipoglicemia/enfermagem , Hipoglicemiantes/uso terapêutico , Qualidade de Vida
2.
Nutrients ; 13(10)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34684518

RESUMO

BACKGROUND: Children and adolescents affected by type 1 diabetes have an increased risk of being overweight or obese and of suffering from cardiometabolic symptoms. AIMS: To retrospectively evaluate the effects of a new complex of polysaccharide macromolecules, Policaptil Gel Retard® (PGR), on auxological and metabolic parameters, glycaemic variability and control parameters in paediatric patients with type 1 diabetes and metabolic syndrome (MetS). PATIENTS AND METHODS: Data for 27 paediatric patients with a diagnosis of type 1 diabetes in conjunction with obesity and MetS of at least 5 years' standing were collected and retrospectively studied. Of these, 16 (median age 12.9, range 9.5-15.8 years) had been adjunctively treated with PGR and 11 (median age 12.6, range 9.4-15.6 years) had not been treated with PGR. Auxological, metabolic and glycaemic control and variability parameters and insulin dosing were compared after 6 months in the two groups. RESULTS: PGR significantly reduced BMI standard deviation score (SDS) (p < 0.005), waist SDS (p < 0.005), HbA1c (p < 0.05) and daily mean insulin dose requirement (p < 0.005). A significant improvement was also observed in the metabolic and glycaemic variability parameters of mean daily blood glucose (BG) levels (p < 0.005), SD of daily BG levels (p < 0.0001), mean coefficient of variation (p < 0.05), LBGI (p < 0.0001), HBGI (p < 0.0001), J-index (p < 0.005), total cholesterol (p < 0.005), HDL-cholesterol (p < 0.005) and LDL-cholesterol (p < 0.005) and triglycerides (p < 0.05). CONCLUSIONS: PGR produces a good auxological and metabolic response in obese patients with MetS who are affected by type 1 diabetes. It led to a significant reduction in BMI SDS, waist SDS and an improvement in glucose control and variability as well as in other MetS parameters. The use of polysaccharide compounds, especially if associated with appropriate dietary changes, may help achieve treatment targets in type 1 diabetes and reduce the risk that patients develop metabolic syndrome.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Obesidade Pediátrica/tratamento farmacológico , Polissacarídeos/administração & dosagem , Adolescente , Glicemia/metabolismo , Índice de Massa Corporal , Criança , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Complexos Multiproteicos , Obesidade Pediátrica/sangue , Obesidade Pediátrica/complicações , Estudos Retrospectivos , Resultado do Tratamento , Triglicerídeos/sangue
3.
Med Clin North Am ; 105(6): 967-982, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688421

RESUMO

Continuous glucose monitoring system is a convenient wearable device that provides glucose readings from the interstitial fluid every few minutes. Continuous glucose monitoring has revolutionized diabetes care. Patients with type 1 diabetes mellitus and type 2 diabetes mellitus, regardless of the type of treatment regimen, can benefit from continuous glucose monitoring. Continuous glucose monitoring systems provide patients with diabetes and their providers with an ambulatory glucose report that summarizes and also gives graphical representations of the glucose data. This wealth of information helps to better understand patients' glycemic patterns, and thereby reduces hemoglobin A1c and hypoglycemia.


Assuntos
Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Aplicativos Móveis , Smartphone
4.
Nutrients ; 13(10)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34684559

RESUMO

Carbohydrate counting (CHC) is the established form of calculating bolus insulin for meals in children with type 1 diabetes (T1DM). With the widespread use of continuous glucose monitoring (CGM) observation time has become gapless. Recently, the impact of fat, protein and not only carbohydrates on prolonged postprandial hyperglycaemia have become more evident to patients and health-care professionals alike. However, there is no unified recommendation on how to calculate and best administer additional bolus insulin for these two macronutrients. The aim of this review is to investigate: the scientific evidence of how dietary fat and protein influence postprandial glucose levels; current recommendations on the adjustment of bolus insulin; and algorithms for insulin application in children with T1DM. A PubMed search for all articles addressing the role of fat and protein in paediatric (sub-)populations (<18 years old) and a mixed age population (paediatric and adult) with T1DM published in the last 10 years was performed. Conclusion: Only a small number of studies with a very low number of participants and high degree of heterogeneity was identified. While all studies concluded that additional bolus insulin for (high) fat and (high) protein is necessary, no consensus on when dietary fat and/or protein should be taken into calculation and no unified algorithm for insulin therapy in this context exists. A prolonged postprandial observation time is necessary to improve individual metabolic control. Further studies focusing on a stratified paediatric population to create a safe and effective algorithm, taking fat and protein into account, are necessary.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Ingestão de Alimentos/fisiologia , Controle Glicêmico/métodos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adolescente , Algoritmos , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Gorduras na Dieta/análise , Proteínas na Dieta/análise , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Hiperglicemia/etiologia , Hiperglicemia/prevenção & controle , Sistemas de Infusão de Insulina , Masculino , Período Pós-Prandial/fisiologia
5.
Elife ; 102021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515636

RESUMO

Laboratory HbA1c does not always predict diabetes complications and our aim was to establish a glycaemic measure that better reflects intracellular glucose exposure in organs susceptible to complications. Six months of continuous glucose monitoring data and concurrent laboratory HbA1c were evaluated from 51 type 1 diabetes (T1D) and 80 type 2 diabetes (T2D) patients. Red blood cell (RBC) lifespan was estimated using a kinetic model of glucose and HbA1c, allowing the calculation of person-specific adjusted HbA1c (aHbA1c). Median (IQR) RBC lifespan was 100 (86-102) and 100 (83-101) days in T1D and T2D, respectively. The median (IQR) absolute difference between aHbA1c and laboratory HbA1c was 3.9 (3.0-14.3) mmol/mol [0.4 (0.3-1.3%)] in T1D and 5.3 (4.1-22.5) mmol/mol [0.5 (0.4-2.0%)] in T2D. aHbA1c and laboratory HbA1c showed clinically relevant differences. This suggests that the widely used measurement of HbA1c can underestimate or overestimate diabetes complication risks, which may have future clinical implications.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Eritrócitos/fisiologia , Hemoglobina A Glicada/química , Hemoglobina A Glicada/provisão & distribuição , Adulto , Idoso , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade
6.
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
7.
Front Endocrinol (Lausanne) ; 12: 703905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447352

RESUMO

Importance: There is no consensus on the impact of the 2020 COVID-19 pandemic lockdown on glycemic control in children and adolescents with type 1 diabetes (T1D) in the US. Aim: To determine the impact of the pandemic lockdown of March 15th through July 6th, 2020 on glycemic control after controlling for confounders. Subjects and Methods: An observational study of 110 subjects of mean age 14.8 ± 4.9 years(y), [male 15.4 ± 4.0y, (n=57); female 14.1 ± 3.8y, (n=53), p=0.07] with T1D of 6.31 ± 4.3y (95% CI 1.0-19.7y). Data were collected at 1-4 months before the lockdown and 1-4 months following the lifting of the lockdown at their first post-lockdown clinic visit. Results: There was no significant change in A1c between the pre- and post-pandemic lockdown periods, 0.18 ± 1.2%, (95% CI -0.05 to 0.41), p=0.13. There were equally no significant differences in A1c between the male and female subjects, -0.16 ± 1.2 vs -0.19 ± 1.2%, p=0.8; insulin pump users and non-pump users, -0.25 ± 1.0 vs -0.12 ± 1.4%, p=0.5; and pubertal vs prepubertal subjects, 0.18 ± 1.3 vs -0.11 ± 0.3%, p=0.6. The significant predictors of decrease in A1c were pre-lockdown A1c (p<0.0001) and the use of CGM (p=0.019). The CGM users had significant reductions in point-of-care A1c (0.4 ± 0.6%, p=0.0012), the CGM-estimated A1c (p=0.0076), mean glucose concentration (p=0.022), a significant increase in sensor usage (p=0.012), with no change in total daily dose of insulin (TDDI). The non-CGM users had significantly increased TDDI (p<0.0001) but no change in HbA1c, 0.06 ± 1.8%, p=0.86. Conclusions: There was no change in glycemic control during the pandemic lockdown of 2020 in US children.


Assuntos
COVID-19/epidemiologia , Diabetes Mellitus Tipo 1/sangue , Controle Glicêmico , Quarentena , Adolescente , Fatores Etários , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , COVID-19/prevenção & controle , Criança , Controle de Doenças Transmissíveis/organização & administração , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/terapia , Feminino , Hemoglobina A Glicada/metabolismo , Controle Glicêmico/instrumentação , Controle Glicêmico/métodos , História do Século XXI , Humanos , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Masculino , Pandemias , Quarentena/organização & administração , Estudos Retrospectivos , Estados Unidos/epidemiologia
9.
Sci Rep ; 11(1): 16656, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404828

RESUMO

To determine whether continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) therapy from near-diagnosis of type 1 diabetes is associated with reduced glycaemic variability (GV) and altered microRNA (miRNAs) expression. Adolescents (74% male) within 3-months of diabetes diagnosis (n = 27) were randomized to CSII (n = 12) or MDI. HbA1c, 1-5-Anhydroglucitol (1,5-AG), high sensitivity C-peptide and a custom TaqMan qPCR panel of 52 miRNAs were measured at baseline and follow-up (median (LQ-UQ); 535 (519-563) days). There were no significant differences between groups in baseline or follow-up HbA1c or C-peptide, nor baseline miRNAs. Mean ± SD 1,5-AG improved with CSII vs. MDI (3.1 ± 4.1 vs. - 2.2 ± - 7.0 mg/ml respectively, P = 0.029). On follow-up 11 miRNAs associated with diabetes vascular complications had altered expression in CSII-users. Early CSII vs. MDI use is associated with lower GV and less adverse vascular-related miRNAs. Relationships with future complications are of interest.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , MicroRNAs/genética , Adolescente , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas , Insulina/administração & dosagem , Masculino
10.
Transplantation ; 105(9): 1980-1988, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34416751

RESUMO

BACKGROUND: Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear. METHODS: In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition. RESULTS: The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM. CONCLUSIONS: Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.


Assuntos
Bactérias/crescimento & desenvolvimento , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Microbioma Gastrointestinal , Controle Glicêmico , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Animais , Bactérias/classificação , Bactérias/genética , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/microbiologia , Disbiose , Fezes/microbiologia , Transplante das Ilhotas Pancreáticas , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ribotipagem , Estreptozocina , Técnicas de Cultura de Tecidos
11.
Endocrinol Diabetes Metab ; 4(3): e00235, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34268453

RESUMO

Objective: We conducted this study to investigate whether the COVID-19 pandemic impacted the rate of DKA and previously identified risk factors in children presenting with T1D. Methods: We performed an extension of a retrospective analysis of all paediatric patients (age ≤ 18) newly diagnosed with T1D within a tertiary care referral centre between 01/01/2017 and 09/14/2020. Demographics, insurance coverage and clinical documents 30 days before their T1D diagnosis were abstracted to assess for symptoms at diagnosis, laboratory values (blood glucose, HbA1c, venous pH and bicarbonate) and any healthcare encounters within 30 days of their diagnosis of T1D. Results: 412 patients with T1D [171 F:241 M; 370 pre-COVID era:42 post-COVID era] were included. The percentages of DKA diagnoses at admission were very similar between the pre-COVID and post-COVID groups (47% vs. 48%), as were the severity (13% vs. 14% mild DKA; 33% vs. 31% moderate or severe DKA). Conclusion: There were no fluctuations in the rate of DKA among paediatric patients newly diagnosed with T1D throughout the coronavirus pandemic in central Pennsylvania.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1/diagnóstico , Cetoacidose Diabética/epidemiologia , Adolescente , Glicemia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Cetoacidose Diabética/sangue , Feminino , Humanos , Masculino , Pandemias , Pennsylvania , Prevalência , Estudos Retrospectivos
12.
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
13.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210000

RESUMO

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM). Enhanced platelet reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin (THPO), a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature platelets by enhancing both activation and binding to leukocytes in response to different agonists. Increased THPO levels have been reported in different clinical conditions characterized by a generalized pro-thrombotic state, from acute coronary syndromes to sepsis/septic shock, and associated with elevated indices of platelet activation. To investigate the potential contribution of elevated THPO levels in platelet activation in T1DM patients, we studied 28 T1DM patients and 28 healthy subjects. We measured plasma levels of THPO, as well as platelet-leukocyte binding, P-selectin, and THPO receptor (THPOR) platelet expression. The priming activity of plasma from diabetic patients or healthy subjects on platelet-leukocyte binding and the role of THPO on this effect was also studied in vitro. T1DM patients had higher circulating THPO levels and increased platelet-monocyte and platelet-granulocyte binding, as well as platelet P-selectin expression, compared to healthy subjects, whereas platelet expression of THPOR did not differ between the two groups. THPO concentrations correlated with platelet-leukocyte binding, as well as with fasting glucose and Hb1Ac. In vitro, plasma from diabetic patients, but not from healthy subjects, primed platelet-leukocyte binding and platelet P-selectin expression. Blocking THPO biological activity using a specific inhibitor prevented the priming effect induced by plasma from diabetic patients. In conclusion, augmented THPO may enhance platelet activation in patients with T1DM, potentially participating in increasing atherosclerotic risk.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Receptores de Trombopoetina/sangue , Trombopoetina/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Monócitos/metabolismo , Selectina-P/sangue , Ativação Plaquetária , Contagem de Plaquetas , Adulto Jovem
14.
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
15.
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
16.
PLoS One ; 16(7): e0254951, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34283880

RESUMO

AIMS: The majority of studies report that the Covid-19 pandemic lockdown did not have a detrimental effect on glycaemia. We sought to explore the impact of lockdown on glycaemia and whether this is sustained following easing of restrictions. METHODS: Retrospective, observational analysis in adults and children with type 1 diabetes attending a UK specialist centre, using real-time or intermittently scanned continuous glucose monitoring. Data from the following 28-day time periods were collected: (i) pre-lockdown; (ii) during lockdown; (iii) immediately after lockdown; and (iv) a month following relaxation of restrictions (coinciding with Government-subsidised restaurant food). Data were analysed for times in glycaemic ranges and are expressed as median (IQR). RESULTS: 145 adults aged 35.5 (25.8-51.3) years with diabetes duration of 19.0 (7.0-29.0) years on multiple daily injections of insulin (60%) and continuous insulin infusion (40%) were included. In adults, % time in range (70-180mg/dL) increased during lockdown (60.2 (45.2-69.3)%) compared to pre-lockdown (56.7 (43.5-65.3)%; p<0.001). This was maintained in the post-lockdown time periods. Similarly, % time above range (>180mg/dL) reduced in lockdown compared to pre-lockdown (p = 0.01), which was sustained thereafter. In children, no significant changes to glycaemia were observed during lockdown. In multivariable analysis, a greater increase in %TIR 3.9-10mmol/L (70-180mg/dL) during lockdown was associated with higher levels of deprivation (coefficient: 4.208, 95% CI 0.588 to 7.828; p = 0.02). CONCLUSIONS: Glycaemia in adults improved during lockdown, with people from more deprived areas most likely to benefit. This effect was sustained after easing of restrictions, with government-subsidised restaurant eating having no adverse impact on glycaemia.


Assuntos
COVID-19/sangue , Diabetes Mellitus Tipo 1/sangue , Adulto , Glicemia/metabolismo , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Feminino , Humanos , Masculino , Pandemias , Estudos Retrospectivos , Reino Unido
17.
Nutr Metab Cardiovasc Dis ; 31(9): 2661-2668, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34218990

RESUMO

BACKGROUND AND AIMS: To investigate diabetes treatment initiation and continuation in the next sixth months in newly diagnosed Italian subjects. METHODS AND RESULTS: We analyzed administrative claims of 11,300,750 Italian residents. Subjects with incident diabetes were identified by glucose lowering drug prescriptions, disease-specific co-payment exemptions and hospital discharge codes occurring in 2018 but not in 2017. Incident cases were 65,932 of whom 91.4% received the prescription of a glucose lowering drug. Among the latter, those receiving a prescription of a noninsulin medication but no insulin were 84.8%, those receiving a prescription of insulin only were 9.4%, and those receiving prescriptions of both insulin and noninsulin drugs were 5.8%. Metformin was the most frequently drug initially prescribed in noninsulin treated subjects (~85%) and sulphonylurea receptor (SUR) agonists collectively ranked as second (~13%). Lispro (35%) and glargine (34%) were the most frequently prescribed molecules in subjects who were insulin treated. Differences in prescriptions were found in age categories, with increased use of SUR agonists across decades. In the first six months, as many as 50% of noninsulin treated patients continued with the initial drug, ~15% added a second agent, ~5% switched to another medication, and ~30% discontinued any glucose lowering treatment. CONCLUSIONS: These data document that current guidelines are often neglected because prescriptions of SUR agonists as first agent are still quite common and insulin is prescribed more than expected. They point out the urgent need to improve the dissemination and implementations of guidelines in diabetes care.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Padrões de Prática Médica/tendências , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/metabolismo , Criança , Pré-Escolar , Bases de Dados Factuais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Prescrições de Medicamentos , Substituição de Medicamentos/tendências , Quimioterapia Combinada/tendências , Uso de Medicamentos/tendências , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Lactente , Recém-Nascido , Insulina/uso terapêutico , Itália/epidemiologia , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Compostos de Sulfonilureia/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Front Immunol ; 12: 628564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211456

RESUMO

Neutrophil extracellular traps (NETs) and mitochondrial DNA (mtDNA) are inflammatory mediators involved in the development of type 1 diabetes (T1D). Pancreas-infiltrating neutrophils can release NETs, contributing to the inflammatory process. Levels of NETs are increased in serum from patients with T1D and mtDNA is increased in adult T1D patients. Our aim was to investigate extracellular DNA (NETs, mtDNA and nuclear DNA) in children with newly diagnosed T1D and in children at high risk of the disease. We also elucidated if extracellular DNA short after diagnosis could predict loss of endogenous insulin production. Samples were analysed for mtDNA and nuclear DNA using droplet digital PCR and NETs were assessed by a NET-remnants ELISA. In addition, in vitro assays for induction and degradation of NETs, as well as analyses of neutrophil elastase, HLA genotypes, levels of c-peptide, IL-1beta, IFN and autoantibodies (GADA, IA-2A, IAA and ZnT8A) were performed. In serum from children 10 days after T1D onset there was an increase in NETs (p=0.007), mtDNA (p<0.001) and nuclear DNA (p<0.001) compared to healthy children. The elevated levels were found only in younger children. In addition, mtDNA increased in consecutive samples short after onset (p=0.017). However, levels of extracellular DNA short after onset did not reflect future loss of endogenous insulin production. T1D serum induced NETs in vitro and did not deviate in the ability to degrade NETs. HLA genotypes and autoantibodies, except for ZnT8A, were not associated with extracellular DNA in T1D children. Serum from children with high risk of T1D showed fluctuating levels of extracellular DNA, sometimes increased compared to healthy children. Therefore, extracellular DNA in serum from autoantibody positive high-risk children does not seem to be a suitable biomarker candidate for prediction of T1D. In conclusion, we found increased levels of extracellular DNA in children with newly diagnosed T1D, which might be explained by an ongoing systemic inflammation.


Assuntos
Núcleo Celular/genética , DNA Mitocondrial/sangue , DNA/sangue , Diabetes Mellitus Tipo 1/sangue , Armadilhas Extracelulares/metabolismo , Adolescente , Fatores Etários , Autoanticorpos/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Medição de Risco , Fatores de Risco , Regulação para Cima
19.
PLoS One ; 16(7): e0254859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34329330

RESUMO

BACKGROUND: Glycocalyx lines the inner surface of the capillary endothelium. Capillaroscopy enables visualization of the sublingual capillaries and measurement of the Perfused Boundary Region (PBR) as an estimate of the glycocalyx. Novel software enables assessment of the PBR estimated at a fixed high flow level (PBR-hf) and an overall microvascular assessment by the MicroVascular Health Score (MVHS). Damaged glycocalyx may represent microvascular damage in diabetes and assessment of its dimension might improve early cardio-renal risk stratification. AIM: To assess the associations between PBR, PBR-hf and MVHS and cardio-renal risk factors in persons with type 1 diabetes (T1D); and to compare these dimensions in persons with T1D and controls. METHODS: Cross-sectional study including 161 persons with T1D stratified according to level of albuminuria and 50 healthy controls. The PBR, PBR-hf and MVHS were assessed by the GlycoCheck device (valid measurements were available in 136 (84.5%) with T1D and in all the controls). Higher PBR and PBR-hf indicate smaller glycocalyx width. Lower MVHS represents a worse microvascular health. RESULTS: There were no associations between PBR, PBR-hf or MVHS and the cardio-renal risk factors in persons with T1D, except for higher PBR-hf and lower MVHS in females (p = 0.01 for both). There was no difference in PBR, PBR-hf or MVHS in persons with normo-, micro- or macroalbuminuria. The PBR was higher (2.20±0.30 vs. 2.03±0.18µm; p<0.001) and MVHS lower (3.15±1.25 vs. 3.53±0.86µm; p = 0.02) in persons with T1D compared to controls (p≤0.02). After adjustment for cardio-renal risk factors the difference in PBR remained significant (p = 0.001). CONCLUSIONS: The endothelial glycocalyx dimension was impaired in persons with T1D compared to controls. We found no association between the endothelial glycocalyx dimension and the level of albuminuria or cardio-renal risk factors among persons with T1D. The use of the GlycoCheck device in T1D may not contribute to cardio-renal risk stratification.


Assuntos
Albuminúria/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Glicocálix/metabolismo , Idoso , Estudos Transversais , Endotélio Vascular , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Fatores de Risco
20.
Diabetes ; 70(8): 1754-1766, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34285121

RESUMO

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes (n = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA1c 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m2) and 10-year historical uACR, HbA1c, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in apolipoprotein E -/- mice. Kidney biopsies were used to examine infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACRAUC0-10yrs, 29.7 ± 8.8 vs. 4.5 ± 0.5; P < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m2 higher estimated glomerular filtration rates (modified Schwartz equation; Padj < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; P < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes showed elevated collagen IV and sodium-glucose cotransporter 2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T-cell production of KIM-1.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/sangue , Receptor Celular 1 do Vírus da Hepatite A/sangue , Rim/patologia , Adolescente , Adulto , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Estudos Retrospectivos , Adulto Jovem
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