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1.
Am J Health Syst Pharm ; 79(7): 547-555, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-34957477

RESUMO

PURPOSE: High-dose insulin/euglycemia (HDIE) is targeted therapy for ß-blocker and calcium channel blocker overdose. A guideline using concentrated insulin infusions (20 units/mL), aggressive monitoring, and supportive recommendations was implemented. We sought to evaluate safety before and after HDIE guideline implementation and describe the patient population, insulin doses, supplemental dextrose, vasopressor use, hospital and intensive care unit (ICU) lengths of stay, and mortality. METHODS: Retrospective review was performed of patients receiving HDIE before and after guideline implementation at an academic medical center and community hospital from March 2011 through December 2019. Information on patient and overdose demographics, ingestion data, vital signs, interventions, adverse events, and disposition was collected. Data are presented descriptively with comparisons using Mann-Whitney U analysis and Fisher's exact tests. RESULTS: During the study period, 27 patients were treated with HDIE, 10 before guideline implementation (37%; mean [SD] initial insulin dose, 0.49 [0.35] units/kg/h; mean [SD] maximum insulin dose, 2.25 [3.29] units/kg/h; median [interquartile range] duration, 10 [5.5-18.75] hours) and 17 after guideline implementation (63%; mean [SD] initial insulin dose, 1.01 [0.34] units/kg/h; mean [SD] maximum insulin dose, 2.99 [5.05] unit/kg/h; median [interquartile range] duration, 16 [11.5-37] hours). Hypoglycemia, hypokalemia, and volume overload occurred in 80% vs 29% (P = 0.018), 40% vs 53% (P = 0.69), and 50% vs 65% (P = 0.69) of patients in the preguideline vs postguideline group, respectively. Most patients received an initial insulin bolus (85%; mean [SD], 70.3 [21.8] units, 0.9 [0.26] units/kg) and vasopressor infusion (85%). More postguideline patients received a dextrose infusion with a concentration of 20% or higher (93% vs 50%, P = 0.015). There were no differences in cardiac arrest, in-hospital mortality, or hospital or ICU length of stay between the groups. CONCLUSION: Hypoglycemia was reduced using an HDIE guideline and concentrated insulin.


Assuntos
Hiperinsulinismo , Hipoglicemia , Antagonistas Adrenérgicos beta , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Hiperinsulinismo/induzido quimicamente , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Insulina
2.
Sheng Li Xue Bao ; 74(2): 255-264, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35503073

RESUMO

The synthesis and decomposition of glycogen adjust the blood glucose dynamically to maintain the energy supply required by the cells. As the only hormone that lowers blood sugar in the body, insulin can promote glycogen synthesis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and increasing glucose transporter translocation, and inhibit gluconeogenesis to lower blood glucose. In the endometrium, glycogen metabolism is active, but gluconeogenesis does not occur. The glycogen metabolism in the endometrium is controlled not only by the classical glucose regulating hormones, but also by the ovarian hormones. The functional activities related to implantation of the endometrium during the implantation window require glucose as energy source. A large amount of glucose is used to synthesize glycogen in the endometrium before implantation, which could meet the increased energy demand for embryo implantation. In diabetes, glycogen metabolism in the endometrium is impaired, which frequently leads to implantation failure and early abortion. This article reviews the glycogen metabolism in the endometrium and discusses its role in embryo implantation, which provide new ideas for embryo implantation research and infertility treatment.


Assuntos
Glicemia , Fosfatidilinositol 3-Quinases , Glicemia/metabolismo , Implantação do Embrião , Endométrio , Feminino , Glucose/metabolismo , Glicogênio/metabolismo , Humanos , Insulina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Gravidez
3.
Eur Rev Med Pharmacol Sci ; 26(8): 2765-2774, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503621

RESUMO

OBJECTIVE: We aimed to classify Japanese adults without diabetes into different categories based on the oral glucose tolerance test (OGTT) and characterize their insulin sensitivity and insulin secretion. PATIENTS AND METHODS: The OGTT was performed on 1,085 Japanese individuals without diabetes (aged 20-64 years); blood glucose and insulin levels were measured at 0, 30-, 60-, 90-, and 120-min. Fasting blood chemistry, hematology, and urine were analyzed. The participants were classified into four categories based on the following: (A) 30 min post-load plasma glucose levels < 157 mg/dL and/or (B) 120 min post-load plasma glucose levels < 126 mg/dL and Matsuda index > 4.97. Category 1 satisfied both conditions, category 2 satisfied condition A but not B, category 3 satisfied condition B but not A, and category 4 satisfied neither condition. RESULTS: Overall, 46%, 21%, 13%, and 20% of the participants were classified into categories 1, 2, 3, and 4, respectively. Compared with category 1, the characteristics of the other categories were: 2, low insulin sensitivity and high blood glucose levels during the later period; 3, low insulin secretion and a rapid increase in blood glucose levels; and 4, combined characteristics of categories 2 and 3. Most blood test values besides glucose metabolism in category 4 were also worse than those in category 1. Categories 1 and 2 had a high proportion of females, whereas categories 3 and 4 had a low proportion. CONCLUSIONS: Japanese adults without diabetes are classified into four categories with different insulin sensitivities and insulin secretion using OGTT results. Each category has different characteristics of age and sex distribution and clinical values besides glucose metabolism.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Resistência à Insulina , Adulto , Glicemia/metabolismo , Diabetes Mellitus/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina , Japão
4.
Eur Rev Med Pharmacol Sci ; 26(8): 2782-2793, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503623

RESUMO

OBJECTIVE: To evaluate the efficacy and safety profile of fixed ratio combinations (FRC) in patients with type 2 diabetes mellitus (DMT2) poorly controlled on different insulin regimens. PATIENTS AND METHODS: This multicentric observational study included 376 patients (157 males, 219 female), with longstanding DMT2 inadequately controlled (HbA1c >7%) on different insulin regimens; premix insulin analogs (MIX) (23.2%), basal-bolus regimen (BB) (30.9%) or basal oral therapy (BOT) (37.1%) to whom FRC was introduced at least 6 months prior to data collection. RESULTS: Median age of patients was 67 years, with the duration of diabetes for 14 years, median HbA1c of 8.4% and BMI of 34.35 kg/m2. The proportion of patients treated with IDegLira and IGlarLixi was similar (48.4% vs. 51.6%). There was a borderline difference regarding regimen groups (p = 0.059) implying the greatest improvement of HbA1c in the MIX group. The significant interaction between BOT and BB/MIX regimens (p = 0.011) was noted indicating the largest reduction of BMI in BB and MIX groups. After the FRC administration, there was no significant difference in gastrointestinal (GIT) side-effects. The number of patients with hypoglycemic episodes decreased from 24% to 7% after FRC initiation (p < .001). The group using IGlarLixi required a significantly higher average dose steps compared to IDegLira (p < .001 for all) to achieve glycemic goals, while a larger proportion of patients using IDegLira lost more than 5 kg, compared to IGlarLixi (p < .001). Significant improvement was observed in all glycemic parameters in all insulin treated patients after replacement of insulin therapy with FRC (p < .001 for all). Composite outcome defined as any weight loss and HbA1c below 7% was accomplished in 20.3% of patients. CONCLUSIONS: In real life setting switching to both FRC options in people with longstanding inadequately controlled DMT2 treated with different insulin regimens could offer an effective therapeutic choice for achieving glycemic goals, with an improved safety profile.


Assuntos
Diabetes Mellitus Tipo 2 , Idoso , Glicemia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes , Insulina/uso terapêutico , Insulina Glargina/efeitos adversos , Masculino , Peptídeos
5.
BMC Pediatr ; 22(1): 245, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501770

RESUMO

BACKGROUND: Obesity usually complicates hypothyroidism. Adipokines like leptin and adiponectin secreted by adipose tissue modulate insulin resistance (IR), appetite, and obesity. The association between adipokines, IR, and thyroid hormone has not been sufficiently studied in children. We investigated leptin and adiponectin as well as IR and their association with thyroid hormone in both lean and hypothyroid children and adolescents with obesity. METHODS: The study included 30 lean hypothyroid, 30 hypothyroid children and adolescents with obesity, and 30 healthy lean children as the control group. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), fasting blood glucose, fasting insulin, homeostatic model assessment method of insulin resistance (HOMA-IR), leptin, and adiponectin levels were estimated in all participants. RESULTS: Fasting insulin, HOMA-IR, and leptin levels were significantly elevated in hypothyroid children compared to the control group; more in hypothyroid children with obesity. In contrast, adiponectin levels were significantly lower in the hypothyroid children with obesity compared to the lean hypothyroid children and controls. HOMA-IR was positively correlated to TSH and BMI but inversely correlated with fT3 and fT4 in hypothyroid children. There was no correlation between IR and either leptin or adiponectin levels. Leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity. CONCLUSION: Insulin resistance and leptin levels are increased in hypothyroid children and adolescents; more in those with obesity. IR is not related to leptin and adiponectin levels, however, leptin and adiponectin levels correlate well with BMI in hypothyroid children and adolescents with obesity. IMPACT: Insulin resistance (IR) and leptin levels increase in hypothyroid children and adolescent; more with obesity. IR is not related to leptin and adiponectin levels, however leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity.


Assuntos
Hipotireoidismo , Resistência à Insulina , Obesidade Pediátrica , Adipocinas , Adiponectina , Adolescente , Criança , Humanos , Insulina , Leptina , Obesidade Pediátrica/complicações , Tireotropina
6.
Artigo em Inglês | MEDLINE | ID: mdl-35504696

RESUMO

INTRODUCTION: We investigated trends in the proportion of diabetes treatment and glycemic control, which may be altered by recent advances in insulin and non-insulin drugs, in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A serial cross-sectional study was performed using a multicenter large-population database from the Japan Diabetes Clinical Data Management study group. Patients with type 2 diabetes who attended clinics belonging to the study group between 2002 and 2018 were included to examine trends in glycated hemoglobin A1c (HbA1c) by treatment group using multivariable non-linear regression model. RESULTS: The proportion of patients with insulin only decreased from 15.0% to 3.6%, patients with insulin+non-insulin drugs increased from 8.1% to 15.1%, patients with non-insulin drugs increased from 50.8% to 67.0%, and those with no drugs decreased from 26.1% to 14.4% from 2002 to 2018, respectively. The HbA1c levels of each group, except for no drugs, continued to decrease until 2014 (unadjusted mean HbA1c (%) from 2002 to 2014: from 7.89 to 7.45 for insulin only, from 8.09 to 7.63 for insulin+non-insulin, and from 7.51 to 6.98 for non-insulin) and remained unchanged thereafter. Among insulin-treated patients, use of human insulin decreased, use of long-acting analog insulin increased, and concomitant use of non-insulin drugs increased (from 35.1% in 2002 to 80.9% in 2018), which included increased use of dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists, and the persistently high use of metformin. CONCLUSIONS: During the past two decades, combined use of insulin and non-insulin drugs increased and glycemic control improved and leveled off after 2014 in Japanese patients with type 2 diabetes. Further studies of the trend in association with age and factors related to metabolic syndrome are necessary to investigate strategies aiming at personalized medicine in diabetes care.


Assuntos
Diabetes Mellitus Tipo 2 , Insulina , Estudos Transversais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/análise , Controle Glicêmico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Insulina Regular Humana , Japão/epidemiologia
7.
PLoS One ; 17(5): e0266472, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35522655

RESUMO

Fetuin-A (Fet-A) is a liver-secreted phosphorylated protein, known to impair insulin signaling, which has been shown to be associated with obesity, insulin resistance, and incident diabetes. Fet-A interacts with the insulin-stimulated insulin receptor (IR) and inhibits IR tyrosine kinase activity and glucose uptake. It has been shown that high glucose increases Fet-A expression through the ERK1/2 signaling pathway. However, factors that downregulate Fet-A expression and their potential mechanisms are unclear. We examined the effect of AMP-activated protein kinase (AMPK) on high-glucose induced Fet-A expression in HepG2 cells, Hep3B cells and primary rat hepatocytes. High glucose increased Fet-A and phosphorylated (Ser312) fetuin-A (pFet-A) expression, which are known to impair insulin signaling. AICAR-induced AMPK activation significantly down-regulated high glucose-induced Fet-A expression and secretion of pFet-A while treatment with Compound C (AMPK inhibitor), SB202190 (p38 MAPK inhibitor) or p38 MAPK siRNA transfection prevented AICAR-induced downregulation of Fet-A expression. In addition, activation of p38 MAPK, by anisomycin, decreased the hepatic expression of Fet-A. Further, we our studies have shown that short-term effect of AICAR-treatment on Fet-A expression was mediated by proteosomal degradation, and long-term treatment of AICAR was associated with decrease in hepatic expression of C/EBP beta, an important transcription factor involved in the regulation of Fet-A. Taken together, our studies implicate a critical role for AMPK-p38 MAPK-C/EBPb-ubiquitin-proteosomal axis in the regulation of the expression of hepatic Fet-A.


Assuntos
Proteínas Quinases Ativadas por AMP , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glucose/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Fosforilação , Ratos , Transdução de Sinais , Ubiquitina-Proteína Ligases/metabolismo , alfa-2-Glicoproteína-HS/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Cell Physiol Biochem ; 56(3): 239-253, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524549

RESUMO

BACKGROUND/AIMS: Correlation between type 2 diabetes and other abnormalities such as obesity with redox balance disturbance was analyzed in many reports. Nonetheless, antioxidants impact on parameters accompanying these conditions is still unknown. Currently the role of redox imbalance in the adipose tissue has gained a lot of attention. METHODS: We investigated the impact of α-lipoic acid (ALA) on plasma glucose and insulin concentrations, oxidative stress and inflammation parameters in the subcutaneous (SAT) and visceral (VAT) adipose tissue of high fat diet-fed (HFD) rats. Male Wistar rats were randomly divided into three groups (n = 6) - control diet (CTRL), HFD and HFD with α-lipoic acid (HFD+ALA). RESULTS: HFD increased body weight, plasma insulin and glucose as well as leads to oxidative stress parameters in the adipose tissue. ALA supplementation reduced body weight and oxidative stress parameters more effectively in the visceral than subcutaneous adipose tissue of insulin resistant rats. CONCLUSION: Insulin resistance led to increased enzymatic and non-enzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory parameters more in VAT than in SAT of insulin resistant rats. Moreover, ALA inhibited HFD consequences mainly in VAT mostly through glutathione (GSH) biosynthesis.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Ácido Tióctico , Tecido Adiposo/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Insulina/metabolismo , Masculino , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico
9.
Orphanet J Rare Dis ; 17(1): 187, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525976

RESUMO

BACKGROUND: In recent years, more studies have observed that patients with Prader-Willi syndrome have lower insulin levels and lower insulin resistance than body mass index-matched controls, which may suggest protected glucose metabolism. METHOD: The PubMed and Web of Science online databases were searched to identify relevant studies published in the English language using the terms "Prader-Willi syndrome" with "glucose", "insulin", "diabetes mellitus", "fat", "adipo*", "ghrelin", "oxytocin", "irisin" or "autonomic nervous system". RESULTS: The prevalence of impaired glucose intolerance, type 2 diabetes mellitus and some other obesity-associated complications in patients with Prader-Willi syndrome tends to be lower when compared to that in general obesity, which is consistent with the hypothetically protected glucose metabolism. Factors including adipose tissue, adiponectin, ghrelin, oxytocin, irisin, growth hormone and the autonomic nervous system possibly modulate insulin sensitivity in patients with Prader-Willi syndrome. CONCLUSION: Although lower insulin levels, lower IR and protected glucose metabolism are widely reported in PWS patients, the causes are still mysterious. Based on existing knowledge, we cannot determine which factor is of utmost importance and what are the underlying mechanisms, and further research is in urgent need.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Síndrome de Prader-Willi , Glucose , Humanos , Insulina , Resistência à Insulina/fisiologia , Obesidade/metabolismo , Síndrome de Prader-Willi/metabolismo
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(4): 462-468, 2022 Apr 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35545341

RESUMO

OBJECTIVES: Patients with classical type 1 diabetes mellitus (T1DM) require lifelong dependence on exogenous insulin therapy due to pancreatic beta-cell destruction and absolute insulin deficiency. T1DM accounts for about 90% of children with diabetes in China, with a rapid increase in incidence and a younger-age trend. Epidemiological studies have shown that the overall glycated haemoglobin (HbA1c) and compliance rate are low in Chinese children with T1DM. Optimal glucose control is the key for diabetes treatment, and maintaining blood glucose within the target range can prevent or delay chronic vascular complications in patients with T1DM. Therefore, this study aims to investigate the glycemic control of children with T1DM from Hunan and Henan Province with flash glucose monitoring system (FGMS), and to explore factors associated with glycemic variability. METHODS: A total of 215 children with T1DM under 14 years old were enrolled continuously in 16 hospitals from August 2017 to August 2020. All subjects wore a FGMS device to collect glucose data. Correlation of HbA1c, duration of diabetes, or glucose scan rates with glycemic variability was analyzed. Glucose variability was compared according to the duration of diabetes, HbA1c, glucose scan rates and insulin schema. RESULTS: HbA1c and duration of diabetes were positively correlated with mean blood glucose, standard deviation of glucose, mean amplitude of glucose excursions (MAGE), and coefficient of variation (CV) of glucose (all P<0.01). The glucose scan rates during FGMS wearing was significantly positively correlated with time in range (TIR) (P=0.001) and negatively correlated with MAGE and mean duration of hypoglycemia (all P<0.01). Children with duration ≤1 year had lower time below range (TBR) and MAGE when compared with those with duration >1 year (all P<0.05). TIR and TBR in patients with HbA1c ≤7.5% were higher (TIR: 65% vs 45%, TBR: 5% vs 4%, P<0.05), MAGE was lower (7.0 mmol/L vs 9.4 mmol/L, P<0.001) than those in HbA1c >7.5% group. Compared to the multiple daily insulin injections group, TIR was higher (60% vs 52%, P=0.006), MAGE was lower (P=0.006) in the continuous subcutaneous insulin infusion group. HbA1c was lower in the high scan rates (≥14 times/d) group (7.4% vs 8.0%, P=0.046), TIR was significantly higher (58% vs 47%, P<0.001), and MAGE was lower (P<0.001) than those in the low scan rate (<14 times/d) group. CONCLUSIONS: The overall glycemic control of T1DM patients under 14 years old in Hunan and Henan Province is under a high risk of hypoglycemia and great glycemic variability. Shorter duration of diabetes, targeted HbA1c, higher glucose scan rates, and CSII are associated with less glycemic variability.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Arritmias Cardíacas , Glicemia , Automonitorização da Glicemia/efeitos adversos , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico
12.
Cell Rep Med ; 3(4): 100592, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35522093

RESUMO

Timothy Kieffer's laboratory has contributed to our knowledge of islet biology and the development of cell-based strategies for insulin replacement for diabetes mellitus. In this Q&A, he discusses his journey in academia and industry and his perspectives on the future challenges and opportunities of this field.


Assuntos
Indústrias , Insulina , Humanos , Insulina/uso terapêutico , Masculino
13.
Front Endocrinol (Lausanne) ; 13: 795225, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528003

RESUMO

In diabetes mellitus (DM) treatment, Continuous Glucose Monitoring (CGM) linked with insulin delivery becomes the main strategy to improve therapeutic outcomes and quality of patients' lives. However, Blood Glucose (BG) regulation with CGM is still hampered by limitations of algorithms and glucose sensors. Regarding sensor technology, current electrochemical glucose sensors do not capture the full spectrum of other physiological signals, i.e., lipids, amino acids or hormones, relaying the general body status. Regarding algorithms, variability between and within patients remains the main challenge for optimal BG regulation in closed-loop therapies. This work highlights the simulation benefits to test new sensing and control paradigms which address the previous shortcomings for Type 1 Diabetes (T1D) closed-loop therapies. The UVA/Padova T1DM Simulator is the core element here, which is a computer model of the human metabolic system based on glucose-insulin dynamics in T1D patients. That simulator is approved by the US Food and Drug Administration (FDA) as an alternative for pre-clinical testing of new devices and closed-loop algorithms. To overcome the limitation of standard glucose sensors, the concept of an islet-based biosensor, which could integrate multiple physiological signals through electrical activity measurement, is assessed here in a closed-loop insulin therapy. This investigation has been addressed by an interdisciplinary consortium, from endocrinology to biology, electrophysiology, bio-electronics and control theory. In parallel to the development of an islet-based closed-loop, it also investigates the benefits of robust control theory against the natural variability within a patient population. Using 4 meal scenarios, numerous simulation campaigns were conducted. The analysis of their results then introduces a discussion on the potential benefits of an Artificial Pancreas (AP) system associating the islet-based biosensor with robust algorithms.


Assuntos
Técnicas Biossensoriais , Diabetes Mellitus Tipo 1 , Glicemia/análise , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina , Sistemas de Infusão de Insulina , Estados Unidos
14.
Front Endocrinol (Lausanne) ; 13: 869899, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528010

RESUMO

In developed countries, diabetes is the leading cause of chronic kidney disease (CKD) and accounts for 50% of incidence of end stage kidney disease. Despite declining prevalence of micro- and macrovascular complications, there are rising trends in renal replacement therapy in diabetes. Optimal glycemic control may reduce risk of progression of CKD and related death. However, assessing glycemic control in patients with advanced CKD and on dialysis (G4-5) can be challenging. Laboratory biomarkers, such as glycated haemoglobin (HbA1c), may be biased by abnormalities in blood haemoglobin, use of iron therapy and erythropoiesis-stimulating agents and chronic inflammation due to uraemia. Similarly, glycated albumin and fructosamine may be biased by abnormal protein turnover. Patients with advanced CKD exhibited heterogeneity in glycemic control ranging from severe insulin resistance to 'burnt-out' beta-cell function. They also had high risk of hypoglycaemia due to reduced renal gluconeogenesis, frequent use of insulin and dysregulation of counterregulatory hormones. Continuous glucose monitoring (CGM) systems measure glucose in interstitial fluid every few minutes and provide an alternative and more reliable method of glycemic assessment, including asymptomatic hypoglycaemia and hyperglycaemic excursions. Recent international guidelines recommended use of CGM-derived Glucose Management Index (GMI) in patients with advanced CKD although data are scarce in this population. Using CGM, patients with CKD were found to experience marked glycemic fluctuations with hypoglycemia due to loss of glucose and insulin during haemodialysis (HD) followed by hyperglycemia in the post-HD period. On the other hand, during peritoneal dialysis, patients may experience glycemic excursions with influx of glucose from dialysate solutions. These undesirable glucose exposure and variability may accelerate decline of residual renal function. Although CGM may improve the quality of glycemic monitoring and control in populations with CKD, further studies are needed to confirm the accuracy, optimal mode and frequency of CGM as well as their cost-effectiveness and user-acceptability in patients with advanced CKD and dialysis.


Assuntos
Diabetes Mellitus , Hipoglicemia , Insuficiência Renal Crônica , Glicemia/metabolismo , Automonitorização da Glicemia/métodos , Diabetes Mellitus/terapia , Feminino , Glucose , Humanos , Insulina , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
16.
Syst Rev ; 11(1): 82, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501872

RESUMO

BACKGROUND: Stem cell transplantation (SCT) has paved the way for treatment of autoimmune diseases. SCT has been investigated in type 1 diabetes mellitus (T1DM) as an autoimmune-based disorder, but previous studies have not presented a comprehensive view of its effect on treatment of T1DM. METHODOLOGY: After registration of the present systematic review and meta-analysis in the PROSPERO, a search was done according to the Cochrane guidelines for evaluation of clinical trials to find eligible clinical trials that investigated the effect of SCT on T1DM (based on ADA® diagnostic criteria) from PubMed, Web of science, Scopus, etc, as well as registries of clinical trials from January 1, 2000, to September 31, 2019. A search strategy was designed using MeSH and EM-tree terms. Primary outcome included the changes in the insulin total daily dose (TDD) (U/kg) level, and secondary outcomes included the changes in the HbA1c, c-peptide, and adjusted HbA1c levels. The Q Cochrane test and I2 statistic were performed to assess the heterogeneity and its severity in primary clinical trials. The Cochrane ROB was used to determine risk of bias, and Cochrane Handbook for Systematic Reviews of Interventions was used in the full text papers. The meta-analysis was accomplished in the STATA software, and the results were shown on their forest plots. Confounders were evaluated by the meta-regression test. RESULTS: A total of 9452 studies were electronically screened, and 35 papers were included for data extraction. The results of this review study showed that 173 (26.5%) diabetic patients experienced insulin-free period (from 1 to 80 months), and 445 (68%) showed reduction in TDD of insulin after the SCT. Combination of hematopoietic stem cell (HSC) with mesenchymal stem cell (MSC) transplantation were significantly associated with improvement of the TDD (SMD: - 0.586, 95% CI: - 1.204/- 0.509, I2: 0%), HbA1c (SMD: - 0.736, 95% CI: - 1.107/- 0.365, I2: 0%), adjusted HbA1c (SMD: - 2.041, 95% CI: - 2.648/- 1.434, I2: 38.4%), and c-peptide (SMD: 1.917, 95% CI: 0.192/3.641, I2: 92.5%) on month 3 of follow-up, while its association had a growing trend from 3 to 12 months after the transplantation. Considering severe adverse events, HSC transplantation accompanied with conditioning could not be suggested as a safe treatment. CONCLUSION: Most of the clinical trials of SCT in T1DM were single arm. Although meta-analysis illustrated the SCT is associated with T1DM improvement, well-designed randomized clinical trials are needed to clarify its efficacy. RECOMMENDATION: Based on the results of this meta-analysis, the MSC and its combination with HSC could be considered as "Safe Cell" for SCT in T1DM. Furthermore, to evaluate the SCT efficacy, calculation of insulin TDD (U/kg/day), AUC of c-peptide, and adjusted HbA1c are highly recommended.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Peptídeo C/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/uso terapêutico
17.
Intern Med J ; 52(5): 876-879, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35538006

RESUMO

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes (T2D). Diabetic ketoacidosis (DKA) is an uncommon, but well recognised, life-threatening complication of SGLT2i. In a retrospective study of patients with T2D undergoing cardiac surgery at our institution, DKA occurred in 15.3% of patients taking SGLT2i at the time of surgery, compared with 0.47% of non-SGLT2i-treated patients. Intravenous insulin in the first 24 h after surgery was associated with a significantly lower risk of DKA in SGLT2i patients. Use of an insulin infusion should be considered in these patients, especially in those who are unable to cease their SGLT2i pre-operatively.


Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Ponte de Artéria Coronária , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Glucose , Humanos , Insulina , Estudos Retrospectivos , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
18.
J Diabetes Res ; 2022: 2042273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35502441

RESUMO

Purpose: Insulin receptor (InsR) sensitizers represent a new type of therapeutic agent for the treatment of diabetes, with 2'-O-methylperlatolic acid (2-O-M) being a potential InsR targeting drug. The purpose of this study was to determine whether 2-O-M functions as an activator of the insulin signaling pathway, regulating glucose hemostasis through the InsR and exerting a glucose-lowering effect in an animal model of diabetes. Methods: SPR-based analyses were used to detect the binding of different concentrations of 2-O-M to the InsR. The protein levels of IR-ß, p-IR, AKT, and p-AKT in Hepa and C2C12 cell lines and liver and muscle tissues were determined by western blotting. Glucose uptake capacity was determined in C2C12 cells. Streptozotocin-induced diabetic mice were randomly divided into four groups: the control, insulin treated, 2-O-M treated, and combined insulin and 2-O-M treated. Mice were injected with 2-O-M or normal saline and the average blood glucose concentration after 120 min, and the serum levels of insulin, glucagon, and C-peptide were measured. Next, qRT-PCR was performed to detect the mRNA expression of genes involved in lipid and glucose metabolism in the liver and muscle tissues. Results: 2-O-M binds to the extracellular domain of the InsR. Moreover, combination treatment with 2-O-M and insulin resulted in significant activation of the insulin signaling pathway in vitro and significant stimulation of the glucose uptake capacity of C2C12 myotubes. In mice with streptozotocin-induced diabetes, 2-O-M significantly prolonged the blood glucose-lowering effect of insulin, significantly reduced the secretion of exogenous insulin, and reduced the blood glucose concentration in vivo. In addition, treatment with 2-O-M alone significantly enhanced the phosphorylation of AKT in muscle tissue, which enhanced glucose uptake in C2C12 myotubes. Further, 2-O-M significantly increased glucagon secretion and enhanced liver gluconeogenesis to prevent hypoglycemia. Conclusion: 2-O-M enhances the hypoglycemic effect of insulin through the insulin signaling pathway and can be used as a complement to insulin. This synergetic effect may lower the required dose of insulin and protect ß cells.


Assuntos
Diabetes Mellitus Experimental , Resistência à Insulina , Animais , Benzoatos , Glicemia , Depsídeos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glucagon , Glucose/farmacologia , Insulina/metabolismo , Resistência à Insulina/fisiologia , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/metabolismo , Salicilatos , Transdução de Sinais , Estreptozocina/farmacologia
19.
Tijdschr Psychiatr ; 64(4): 220-225, 2022.
Artigo em Holandês | MEDLINE | ID: mdl-35506975

RESUMO

The combination of an eating disorder and diabetes mellitus type 1 is a serious double diagnosis. Compensation behavior is often present in the form of insulin restriction which can have debilitating health consequences. Studies on prevalence, diagnosis and mortality are well documented but literature regarding evidence-based treatments is limited. In this article we describe a case study of a patient with diabetes who was admitted to our treatment unit for eating disorders due to manipulation of her diabetes medication. On the basis of this case and a literature study, we conclude that the standard treatment for eating disorders is insufficient for this double diagnosis. An adapted treatment, aimed at both the eating disorder and the diabetes is necessary to increase the chance of recovery.


Assuntos
Diabetes Mellitus Tipo 1 , Transtornos da Alimentação e da Ingestão de Alimentos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/terapia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Feminino , Humanos , Insulina/uso terapêutico , Prevalência
20.
JAMA Netw Open ; 5(5): e2210464, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35507342

RESUMO

Importance: Insulin pumps improve glycemic control and quality of life in children with type 1 diabetes (T1D). Canada's provinces have implemented universal pediatric programs to improve access. However, these programs provide differing financial coverage, allowing for unique cross-jurisdictional comparisons. Objective: To evaluate possible socioeconomic status (SES) disparities in pump uptake in Québec, where pumps are fully funded, with those in Manitoba, where pumps are partially funded. Design, Setting, and Participants: Using health administrative databases and a clinical registry, parallel, population-based cohort studies of children with diabetes were conducted from April 1, 2011, in Québec, and April 1, 2012, in Manitoba, until March 31, 2017. In analysis conducted from July 1, 2019, to November 30, 2021, multivariable Cox proportional hazards regression models were applied to study the association between pump uptake and SES, defined using validated area-based material and social deprivation indices. Children aged 1 to 17 years with T1D were identified using a validated definition in administrative data (Québec) and a clinical registry (Manitoba). Those using pumps before the initiation of provincial programs were excluded. Exposures: Socioeconomic status. Main Outcomes and Measures: Insulin pump uptake. Results: A total of 2919 children with T1D were identified in Québec: 1550 male (53.1%), mean (SD) age at diagnosis, 8.3 (4.4) years, and 1067 (36.6%) were using a pump. In Manitoba, 636 children were identified: 364 male (57.2%), mean (SD) age at diagnosis, 8.8 (4.4) years, and 106 (16.7%) were using a pump. In Québec, the mean age at diagnosis of T1D was lower in children using the pump compared with those not using a pump (7.6 [4.1] vs 8.7 [4.5] years); sex distribution was similar (562 [52.7%] vs 988 [53.3%] male). No differences in mean (SD) age at diagnosis (8.8 [4.4] vs 8.8 [4.3] years) or sex (57 [53.8%] vs 307 [57.9%] male) were noted in both groups in Manitoba. Increasing material deprivation was associated with decreased pump uptake in both Québec (adjusted hazard ratio [aHR] 0.89; 95% CI, 0.85-0.93) and Manitoba (aHR, 0.70; 95% CI, 0.60-0.82). Inclusion of ethnic concentration did not change this association. Socioeconomic disparities in pump uptake were greater in Manitoba than Québec (P = .006 by t test; Cochran Q, 8.15; P = .004; I2 = 87.7%; 95% CI, 52.5%-96.8%). Conclusions and Relevance: The results of this study suggest that the program of full coverage for pumps available in Québec partially mitigates observed SES disparities in uptake and may be a model to improve access for all children with T1D.


Assuntos
Diabetes Mellitus Tipo 1 , Canadá/epidemiologia , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Humanos , Insulina/uso terapêutico , Masculino , Qualidade de Vida , Classe Social
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