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BACKGROUND: The management of multidrug-resistant tuberculosis (MDR-TB) remains challenging. Treatment outcome is influenced by multiple factors; the specific roles of diabetes and glycemic control remain uncertain. This study aims to assess the impact of glycemic control on drug exposure, to investigate the association between drug exposure and treatment outcomes, and to identify clinically significant thresholds predictive of treatment outcome, among patients with diabetes. METHODS: This multicenter prospective cohort study involved patients with confirmed MDR-TB and diabetes. Drug exposure level was estimated by noncompartmental analysis. The minimum inhibitory concentrations (MICs) were determined for the individual Mycobacterium tuberculosis isolates. The influence of poor glycemic control (glycated hemoglobin ≥7%) on drug exposure and the associations between drug exposure and treatment outcome were evaluated by univariate and multivariate analysis. Classification and regression tree analysis was used to identify the drug exposure/susceptibility thresholds. RESULTS: Among the 131 diabetic participants, 43 (32.8%) exhibited poor glycemic control. Poor glycemic control was independently associated with decreased exposure to moxifloxacin, linezolid, bedaquiline, and cycloserine, but not clofazimine. Additionally, a higher ratio of drug exposure to susceptibility was found to be associated with a favorable MDR-TB treatment outcome. Thresholds predictive of 6-month culture conversion and favorable outcome were bedaquiline area under the concentration-time curve (AUC)/MIC ≥245 and moxifloxacin AUC/MIC ≥67, demonstrating predictive accuracy in patients, regardless of their glycemic control status. CONCLUSIONS: Glycemic control and optimal TB drug exposure are associated with improved treatment outcomes. This dual management strategy should be further validated in randomized controlled trials of patients with MDR-TB and diabetes.
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Antituberculosos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Masculino , Feminino , Estudos Prospectivos , Antituberculosos/uso terapêutico , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Resultado do Tratamento , Mycobacterium tuberculosis/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Moxifloxacina/uso terapêutico , Linezolida/uso terapêutico , Ciclosserina/uso terapêutico , Diarilquinolinas/uso terapêutico , Idoso , Clofazimina/uso terapêutico , Hemoglobinas Glicadas/análiseRESUMO
Reducing the high risk of recurrent stroke in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) has proven to be challenging, but aggressive medical management, with intensive risk factor control and antithrombotic therapy, has been shown to be beneficial. High-intensity statins are recommended for patients with atherosclerotic stroke, including sICAS. Ezetimibe and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are beneficial for those who fail to reach low-density lipoprotein targets or those with statin intolerance. The treatment target for sICAS is low-density lipoprotein <70 mg/dL. In neurologically stable patients, blood pressure should be treated to goal <140/90 mmâ Hg with the use of thiazide diuretics, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers preferentially. For those with diabetes, treat to goal hemoglobin A1C ≤7% for most patients through combination of diet, insulin, and hypoglycemic drugs. Some degree of physical activity (eg, walking, stationary biking with arms or legs, etc) should be encouraged in all patients with sICAS who are not severely disabled. A minimum of 10 minutes of moderate-intensity aerobic activity 4 times a week is recommended for patients who are capable of exercise. For all patients with severe sICAS (70%-99% stenosis), dual antiplatelet therapy for up to 90 days followed by single antiplatelet agent is recommended.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Acidente Vascular Cerebral , Humanos , Constrição Patológica , Pró-Proteína Convertase 9 , Acidente Vascular Cerebral/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteínas LDLRESUMO
The Japan Diabetes Society and the Japan Cancer Association launched a joint committee and published their "First Joint Committee Report on Diabetes and Cancer" in 2013, compiling recommendations for physicians and health-care providers as well as for the general population. In 2016, the "Second Joint Committee Report on Diabetes and Cancer" summarized the current evidence on glycemic control and cancer risk in patients with diabetes. The current "Third Joint Committee Report on Diabetes and Cancer", for which the joint committee also enlisted the assistance of the Japanese Society of Clinical Oncology and the Japanese Society of Medical Oncology, reports on the results from the questionnaire survey, "Diabetes Management in Patients Receiving Cancer Therapy," which targeted oncologists responsible for cancer management and diabetologists in charge of glycemic control in cancer patients. The results of the current survey indicated that there is a general consensus among oncologists and diabetologists with regard to the need for guidelines on glycemic control goals, the relevance of glycemic control, and glycemic control during cancer therapy in cancer patients.
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Diabetes Mellitus , Neoplasias , Oncologistas , Médicos , Humanos , Japão/epidemiologia , Diabetes Mellitus/epidemiologia , Neoplasias/epidemiologia , Neoplasias/terapia , Inquéritos e QuestionáriosRESUMO
We aim to examine the association of sleep duration, sleep quality, late chronotype, and circadian misalignment with glycemic control and risk of complications in young adults with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Self-reported sleep duration, quality, timing, and circadian misalignment were assessed via a modified Pittsburgh Sleep Quality Index (PSQI) questionnaire, and chronotype was assessed via the Morningness-Eveningness Questionnaire (MEQ). We examined diabetes complications including loss of glycemic control (defined as hemoglobin A1c ≥8%), hypertension, dyslipidemia, albuminuria, and diabetic peripheral neuropathy. Multivariable logistic regression models were constructed to assess associations between sleep and circadian measures with outcomes of interest, such as loss of glycemic control and diabetes complications. A total of 421 participants (34.2% male), mean age 23.6 ± 2.5 yr, mean body mass index (BMI) of 36.1 ± 8.3 kg/m2, and mean diabetes duration of 10.0 ± 1.5 yr were evaluated. Self-reported short sleep duration, daytime sleepiness, and sleep quality were not associated with loss of glycemic control or diabetes complications. Late self-reported bedtime (after midnight) on work/school nights, rather than self-expressed chronotype or circadian misalignment, was independently associated with loss of glycemic control. An association was seen between late bedtimes and albuminuria but was attenuated after adjusting for depression. In conclusion, late bedtime on work/school days, rather than short sleep duration, daytime sleepiness, or poor sleep quality, was independently associated with loss of glycemic control in this longitudinal cohort of young adults with youth-onset type 2 diabetes.NEW & NOTEWORTHY The prevalence of type 2 diabetes in youth is increasing at an alarming rate. Identifying potentially modifiable factors modulating glycemic control is critically important to reduce micro and macrovascular complications. In a large cohort of youth-onset type 2 diabetes, self-reported late bedtime on work/school days was independently associated with loss of glycemic control in this longitudinal cohort of young adults with youth-onset type 2 diabetes.
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Glicemia , Ritmo Circadiano , Diabetes Mellitus Tipo 2 , Controle Glicêmico , Autorrelato , Sono , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Adulto Jovem , Glicemia/metabolismo , Adulto , Qualidade do Sono , Hemoglobinas Glicadas/metabolismo , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/sangue , Fatores de Tempo , Adolescente , Fatores de Risco , Biomarcadores/sangueRESUMO
Recent studies suggested that successful clearance of chronic Hepatitis C Virus (HCV) by using direct-acting antiviral (DAA) agents could improve glycemic control in patients with diabetes; however, some studies failed to identify this benefit. We conducted a systematic review and meta-analysis to assess the impact of sustained virologic response (SVR) after treatment with DAA agents on glycemic control. Embase, Scopus and PubMed were searched through March 26th, 2023, for all studies evaluating whether eradication of HCV infection with DAAs is associated with an impact on glycemic control. Only studies with data on glycemic control, including haemoglobin A1c (HbA1c), fasting glucose, or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), at least 12-week post-SVR were included. Sixteen studies met our eligibility criteria and were included in qualitative analysis. The mean HbA1c was 8.05% (95% CI: 7.79%-8.31%) before treatment and 7.19% (95% CI: 6.98%-7.39%) after treatment. There was a significant mean absolute reduction in HbA1c of 0.72% (95% CI: 0.52%-0.93%) with high heterogeneity between studies (I2 = 91.7%). The reduction in HbA1c remained significant in the subgroup analysis at 3 months follow up post SVR [0.74% (95% CI: 0.57%-0.91%)] and at least 6 months follow up [0.66% (95% CI: 0.23%-1.10%)]. We found a significant reduction in HbA1C after SVR in patients with type 2 diabetes mellitus, reflecting better glycemic control with HCV eradication. This data highlights an important extrahepatic benefit of HCV eradication.
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BACKGROUND: The role of triglyceride-glucose (TyG) index, an insulin resistance indicator, in glycemic management for diabetic patients with coronary artery disease (CAD) was still unknown. Therefore, we aimed to explore the association between glycemic control and cardiovascular (CV) outcomes in patients with diabetes and CAD according to different TyG index levels. METHODS: A total of 9996 diabetic patients with angiograph-proven CAD were consecutively recruited from 2017 to 2018 at Fuwai Hospital. Patients were assigned into 3 groups according to TyG index tertiles (T) (T1: <8.895; T2: 8.895-9.400; T3: ≥9.400). According to American Diabetes Association guidelines, controlled glycemia was defined as targeting glycosylated hemoglobin Alc (HbA1c) < 7%. The primary endpoint was CV events including CV death, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median 3-year follow-up, 381 (3.8%) CV events occurred. Overall, high TyG index (T3) was associated with increased risk of CV events (hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.02-1.94) compared with the lowest TyG index (T1) after multivariable adjustment. Upon stratification by the TyG index, in fully adjusted models, controlled glycemia was associated with reduced risk of CV events in the high TyG index (T3) subgroup (HR: 0.64; 95%CI: 0.42-0.96) but not in the low (T1; HR: 0.79; 95%CI: 0.53-1.16) and moderate (T2; HR: 0.84; 95%CI: 0.56-1.25) TyG index subgroups. CONCLUSIONS: Controlled glycemia was associated with improved CV outcomes in patients with diabetes and established CAD, especially in those with high TyG index levels. Our study, for the first time, provided valuable information that TyG index could help making risk stratification on the glycemic management in diabetic patients with CAD.
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Doença da Artéria Coronariana , Diabetes Mellitus , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Controle Glicêmico , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , GlucoseRESUMO
Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i.
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Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Extremidade Inferior , Doença Arterial Periférica , Comportamento de Redução do Risco , Humanos , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Extremidade Inferior/irrigação sanguínea , Resultado do Tratamento , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Valor Preditivo dos Testes , Fatores de Risco , Medição de Risco , Biomarcadores/sangue , Tomada de Decisão ClínicaRESUMO
BACKGROUND: We assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials. METHODS: Data from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223). RESULTS: In the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (- 0.94% vs. -0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs. CONCLUSIONS: The glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function. TRIAL REGISTRATION: Not applicable (pooled analysis).
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Diabetes Mellitus Tipo 2 , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Compostos Benzidrílicos/efeitos adversos , Glicemia , Glucose , Rim , Método Duplo-CegoRESUMO
BACKGROUND: Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear. SUMMARY: Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry "cargo" (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes. KEY MESSAGE: Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases.
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Doenças Cardiovasculares , Vesículas Extracelulares , Resistência à Insulina , Insulina , Humanos , Vesículas Extracelulares/metabolismo , Animais , Insulina/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Transdução de Sinais , Glicemia/metabolismo , Rigidez Vascular , Exercício FísicoRESUMO
BACKGROUND: A healthy eating pattern such as the Mediterranean-style healthy eating pattern (MED-HEP) is associated with favorable effects on both cardiometabolic risk markers and self-reported health outcomes. Limited evidence exists regarding the influence of the glycemic index (GI) of carbohydrate foods consumed within a healthy eating pattern on self-reported health status and sleep. OBJECTIVES: To investigate the effects of a low- compared with high-GI MED-HEP on changes in health-related quality of life (HRQoL) and sleep. METHODS: The MEDGICarb-intervention trial is a 12-wk randomized, controlled, parallel multi-center trial in adults with ≥2 features of the metabolic syndrome. Participants consumed an eu-energetic diet profiled as a MED-HEP with either low GI (experimental) or high GI (control). HRQoL and sleep were measured with Medical Outcomes Study 36-item short-form health survey version 2, Pittsburgh sleep quality index, and Epworth Sleepiness Scale at baseline and postintervention. RESULTS: One hundred and sixty adults with ≥2 features of the metabolic syndrome completed the intervention [53% females, age 56 ± 10 y, body mass index (kg/m2) 31.0 ± 3.1]. Low- compared with high-GI MED-HEP resulted in differential changes between the groups in the HRQoL domains role physical [5.6 ± 2.2 arbitrary units (AU) compared with -2.5 ± 2.5 AU) and vitality (6.9 ± 1.7 AU compared with 0.0 ± 1.8 AU] (P < 0.05), which were driven mostly by improvements in the low-GI group. There were no significant differences between the MED-HEPs for changes in aggregated physical or mental components or for the other individual domains of HRQoL (physical functioning, bodily pain, general health, social functioning, role emotional, and mental health) or for sleep quality or daytime sleepiness. CONCLUSIONS: Low compared to high GI in the context of a MED-HEP resulted in modest improvements in some, but not all, health domains of HRQoL. No major differences were seen between the groups for measures of sleep. This trial was registered at clinicaltrials.gov as NCT03410719.
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BACKGROUND: A large body of literature associated extra virgin olive oil (EVOO) consumption with low risk of cardiovascular disease and mortality. However, findings from clinical trials related to EVOO consumption on blood pressure, lipid profile, and anthropometric and inflammation parameters are not univocal. OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate the effect of EVOO consumption on cardiometabolic risk factors and inflammatory mediators. METHODS: We searched PubMed/MEDLINE, Scopus, and Cochrane up through 31 March, 2023, without any particular language limitations, in order to identify randomized controlled trials (RCTs) that examined the effects of EVOO consumption on cardiometabolic risk factors, inflammatory mediators, and anthropometric indices. Outcomes were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) estimated from Hedge's g and random-effects modeling. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). RESULTS: Thirty-three trials involving 2020 participants were included. EVOO consumption was associated with a significant decrease in insulin (n = 10; SMD: -0.28; 95% CI: -0.51, -0.05; I2 = 48.57%) and homeostasis model assessment of insulin resistance levels (HOMA-IR) (n = 9; SMD: -0.19; 95% CI: -0.35, -0.03; I2 = 00.00%). This meta-analysis indicated no significant effect of consuming EVOO on fasting blood glucose, triglycerides, total cholesterol, low density lipoproteins, very low density lipoproteins, high density lipoproteins, Apolipoprotein (Apo) A-I and B, lipoprotein a, blood pressure, body mass index, waist circumference, waist to hip ratio, C-reactive protein, interleukin-6, interleukin-10, and tumor necrosis factor α levels (P > 0.05). CONCLUSIONS: The present evidence supports a beneficial effect of EVOO consumption on serum insulin levels and HOMA-IR. However, larger well-designed RCTs are still required to evaluate the effect of EVOO on cardiometabolic risk biomarkers. This study was registered in PROSPERO as CRD42023409125.
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Doenças Cardiovasculares , Insulinas , Humanos , Azeite de Oliva , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Cardiovasculares/prevenção & controle , Mediadores da InflamaçãoRESUMO
BACKGROUND: Continuous glucose monitors provide detailed information regarding glycemic control in pregnant patients with type 1 diabetes. Little data have been published examining the association between continuous glucose monitor parameters and perinatal outcomes among gravidas with type 1 diabetes using continuous glucose monitors. OBJECTIVE: This study aimed to examine the association between perinatal outcomes and time-in-range as assessed by continuous glucose monitors used in pregnant individuals with type 1 diabetes. We hypothesized that higher time-in-range would be associated with lower risk of adverse perinatal outcomes. STUDY DESIGN: This multicenter retrospective cohort study included all gravidas with type 1 diabetes using continuous glucose monitors who delivered from 2020 to 2022 at 5 University of California sites. Only those with continuous glucose monitor target range set to 70 to 140 mg/dL (±10 mg/dL) were included. Time-in-range (%) was recorded at 12, 16, 20, 24, 28, and 32 weeks. The primary maternal and neonatal outcomes were preeclampsia and large for gestational age, defined as birthweight ≥95th percentile. Kruskal-Wallis tests were used to compare median time-in-range between those with and without the primary outcomes. Log-binomial regression was used to obtain risk ratios, with adjustment for microvascular disease and years with type 1 diabetes. RESULTS: A total of 91 patients were included. Most used an insulin pump (81%) and did not have diabetic microvascular disease (72%). Median time since diagnosis of type 1 diabetes was 16 years, and median periconception hemoglobin A1c was 6.7%. Compared with those with preeclampsia, normotensive gravidas had significantly higher time-in-range at nearly every time point. A similar pattern was observed for those with normal-birthweight infants compared with large-for-gestational-age infants. On adjusted analyses, every 5-unit increase in time-in-range at 12 weeks was associated with 45% and 46% reductions in the risks of preeclampsia and large for gestational age, respectively (preeclampsia: adjusted risk ratio, 0.55; 95% confidence interval, 0.30-0.99; large for gestational age: adjusted risk ratio, 0.54; 95% confidence interval, 0.29-0.99). CONCLUSION: Higher time-in-range is associated with lower risk of preeclampsia and large for gestational age. This association is observed early in gestation, when each 5-unit increase in time-in-range is associated with â¼50% reduction in the risk of these complications. These findings can be used to counsel patients regarding the risk of pregnancy complications at specific time-in-range values, and to encourage patients that even small improvements in time-in-range can have significant impact on pregnancy outcomes. Larger studies are needed to further explore these findings and to identify optimal time-in-range to reduce perinatal complication rates.
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PURPOSE: We undertook a study to investigate the relationship between duration of medication use and prevalence of impaired awareness of hypoglycemia (IAH) among patients with insulin-treated or sulfonylurea-treated type 2 diabetes in Taiwan. METHODS: A total of 898 patients (41.0% insulin users, 65.1% sulfonylurea users; mean [SD] age = 59.9 [12.3] years, 50.7% female) were enrolled in pharmacies, clinics, and health bureaus of Tainan City, Taiwan. Presence of IAH was determined with Chinese versions of the Gold questionnaire (Gold-TW) and Clarke questionnaire (Clarke-TW). Sociodemographics, disease and treatment histories, diabetes-related medical care, and health status were collected. We used multiple logistic regression models to assess the relationship between duration of medication use and IAH. RESULTS: Overall IAH prevalence was 41.0% (Gold-TW) and 28.2% (Clarke-TW) among insulin users, and 65.3% (Gold-TW) and 51.3% (Clarke-TW) among sulfonylurea users. Prevalence increased with the duration of sulfonylurea use, whereas it decreased with the duration of insulin use. After controlling for potential confounders, 5 or more years of sulfonylurea use was significantly associated with 3.50-fold (95% CI, 2.39-5.13) and 3.06-fold (95% CI, 2.11-4.44) increases in the odds of IAH based on the Gold-TW and Clarke-TW criteria, respectively. On the other hand, regular blood glucose testing and retinal examinations were associated with reduced odds in both insulin users and sulfonylurea users. CONCLUSIONS: The prevalence of IAH was high among patients using sulfonylureas long term, but the odds of this complication were attenuated for those who received regular diabetes-related medical care. Our study suggests that long-term sulfonylurea use and irregular follow-up increase risk for IAH. Further prospective studies are needed to confirm the observed associations.Annals Early Access article.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Hipoglicemiantes , Insulina , Compostos de Sulfonilureia , Humanos , Compostos de Sulfonilureia/uso terapêutico , Compostos de Sulfonilureia/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Idoso , Insulina/uso terapêutico , Prevalência , Modelos Logísticos , Inquéritos e Questionários , Fatores de Tempo , Conhecimentos, Atitudes e Prática em Saúde , Estudos TransversaisRESUMO
A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (ß-cell Tx; n = 51) to control T1D patients (n = 272). Fear of coronavirus infection was higher in those with ß-cell Tx than without (Visual Analogue Scale 5.0 (3.0-7.0) vs. 3.0 (2.0-5.0), p = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, p < 0.001). A previous ß-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with ß-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. -1.72 ± 6.15 mmol/mol, p = 0.006; ΔTime-In-Range during continuous glucose monitoring -4.5% (-6.0%-1.5%) vs. +3.0% (-2.0%-6.0%), p = 0.038). Fewer patients with ß-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, p = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with ß-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control. This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205).
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Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Transplante das Ilhotas Pancreáticas , Feminino , Humanos , Masculino , Ansiedade , Glicemia , Automonitorização da Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/cirurgia , Controle Glicêmico , Pandemias , Saúde PúblicaRESUMO
BACKGROUND: Patients with type 2 diabetes (T2D) are at an increased risk of genital urinary (GU) infections, with the risk increasing with higher A1Cs. Given the broad adoption of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in patients with T2D, both providers and patients need to be aware of common adverse effects associated with these medications, specifically GU infections. However trials involving SGLT2is looked at patients with an average A1C of less than 9%, and thus, the incidence of GU infections may not truly reflect the general diabetic population. OBJECTIVE: The purpose of this study is to assess the association between GU infections in patients started on SGLT2is and A1C levels. METHODS: A retrospective study was conducted on patients seen in an adult, primary care clinic, at New York City Health and Hospitals, South Brooklyn Health. Men and nonpregnant, nonlactating women >18 years old with a diagnosis of T2D who were initiated on an SGLT2i between January 2018 and January 2023 were included in the analysis. The primary endpoint is to compare the risk of GU infections in patients with T2D who were started on SGLT2is, regardless of dose, with hemoglobin A1C of >9% to those with hemoglobin A1C <9% at baseline. RESULTS: Three hundred and twenty-eight patients were eligible based on specified inclusion and exclusion criteria. Overall, there was a statistically significant difference in the number of GU infections that occurred in patients with a baseline A1C >9% compared with those with an A1C <9% (95% confidence interval [CI] = 1.05-2.88; P = 0.041). CONCLUSIONS AND RELEVANCE: Type 2 diabetes patients initiated on SGLT2is may experience an increased risk of GU infection, especially in those patients with an A1C of 9% or greater. Further research is necessary to validate and expand upon these findings.
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OBJECTIVES: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk. METHODS: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling. RESULTS: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%). CONCLUSIONS: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Aborto Induzido , Diabetes Gestacional , Cardiopatias Congênitas , Feminino , Gravidez , Humanos , Hemoglobinas Glicadas , Cardiopatias Congênitas/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: Reduction of major atherosclerotic cardiovascular events (MACE) has not been consistent among different glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess the association between the magnitude of glycemic control, body weight loss, and reductions in systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) achieved through GLP-1 RA therapy and MACE. METHODS: Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through March 2023. Studies were eligible if they were cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs versus placebo in T2DM patients. The outcome of interest was 3-point MACE - cardiovascular death, myocardial infarction, or stroke. Random-effects meta-regression analyses evaluated the associations between reductions of HbA1c, body weight, SBP and LDL-C and reduction of MACE. RESULTS: Overall, 8 CVOTs were included (60079 patients, 30693 with GLP-1 RAs). Reductions of HbA1C were associated with the reduction of 3P-MACE (Log RR -0.290 [95% CI -0.515;-0.064], p = 0.012), with an estimated RR reduction of 25% for each 1% absolute reduction in HbA1C levels. Body weight loss was associated with the reduction of 3P-MACE (Log RR -0.068 [95% CI -0.135;-0.001], p = 0.047), with an estimated RR reduction of 7% for each 1 kg reduction in body weight. Reductions of SBP (Log RR -0.058 [95% CI -0.192;0.076], p = 0.396) and LDL-C (Log RR -0.602 [95% CI -4.157;2.953], p = 0.740) were not associated with the reduction of 3P-MACE. CONCLUSIONS: In T2DM patients, more potent GLP-1 RAs in reducing HbA1c and body weight were associated with greater reductions of MACE.
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Research has indicated that sex hormone-binding globulin (SHBG) is associated with glucose homeostasis and may play a role in the etiology of type 2 diabetes (T2D). While it is unclear whether SHBG may mediate sex differences in glucose control and subsequently, incidence of T2D. We used observational data from the German population-based KORA F4 study (n = 1937, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1387). T2D was initially assessed by self-report and validated by contacting the physicians and/ or reviewing the medical charts. Mediation analyses were performed to assess the role of SHBG in mediating the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis). After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower fasting glucose levels compared to men (ß = -4.94 (mg/dl), 95% CI: -5.77, -4.11). SHBG levels were significantly higher in women than in men (ß = 0.47 (nmol/l), 95% CI:0.42, 0.51). Serum SHBG may mediate the association between sex and fasting glucose levels with a proportion mediated (PM) of 30% (CI: 22-41%). Also, a potential mediatory role of SHBG was observed for sex differences in incidence of T2D (PM = 95% and 63% in models 1 and 2, respectively). Our novel findings suggest that SHBG may partially explain sex-differences in glucose control and T2D incidence.
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The circulating micronutrient pattern in type 2 diabetes mellitus (T2DM) may impact glycemic control and insulin resistance; however, there is a scarcity of studies that have evaluated the circulating micronutrient pattern in the T2DM population. Therefore, our objective was to identify circulating micronutrient pattern and their association with markers of glycemic control and insulin resistance in individuals with T2DM. We developed a cross-sectional observational study involving adults with T2DM in Sergipe, Brazil. We assessed plasma levels of magnesium, zinc, calcium, potassium, and serum 25-hydroxyvitamin D. Additionally, also measured fasting glucose levels, the percentage of glycated hemoglobin (%HbA1c), and calculated the homeostatic model assessment for insulin resistance (HOMA-IR). Patterns of body reserve were established using principal component analysis and categorized into quartiles. Binary logistic regression models were employed. We evaluated 114 individuals (63.7% women), with a median age and body mass index of 49 years and 29.6 kg/m², respectively. Two circulating micronutrient patterns were identified, explaining 62.5% of the variance: Pattern 1 (positive contributions from magnesium, zinc, calcium, and potassium) and Pattern 2 (positive contributions from 25-hydroxyvitamin D and zinc, with a negative contribution from potassium). Lowest quartile for Pattern 1 and Pattern 2 exhibiting a 4.32-fold (p = 0.019) and 3.97-fold (p = 0.038) higher likelihood of increasing HOMA-IR and %HbA1c values, respectively, compared to the larger quartiles. However, no associations were found between these patterns and fasting glucose values. Lowest quartile for both patterns of micronutrients was associated with inadequate metabolic control in individuals with T2DM.
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Diabetes Mellitus Tipo 2 , Controle Glicêmico , Resistência à Insulina , Oligoelementos , Adulto , Feminino , Humanos , Masculino , Glicemia/análise , Glicemia/metabolismo , Cálcio , Estudos Transversais , Glucose , Hemoglobinas Glicadas , Insulina , Magnésio , Micronutrientes , Potássio , ZincoRESUMO
BACKGROUND: Uncontrolled type 2 diabetes mellitus (UT2DM) and its associated consequences nowadays have been a global health crisis, especially for adults. Iron has the property to oxidize and reduce reversibly, which is necessary for metabolic processes and excess accumulation of iron indicated by serum ferritin levels could have a significant impact on the pathophysiology of T2DM via generation of reactive oxygen species (ROS). However, no conclusive evidence existed about the association of serum ferritin with the state of glycemic control status. Therefore, this study aimed to evaluate serum ferritin levels and associated factors in uncontrolled T2DM patients and compare them with those of controlled T2DM and non-diabetic control groups. METHODS: A hospital-based comparative cross-sectional study was conducted among conveniently selected 156 study participants, who were categorized into three equal groups of uncontrolled T2DM, controlled T2DM, and non-diabetic control groups from October 2 to December 29, 2023 at St. Paul's Hospital Millennium Medical College. A pre-tested structured questionnaire was used to collect socio-demographic and diabetes-related information. The laboratory tests were done using an automated chemistry analyzer and IBM-SPSS statistical software (version-27) was utilized for data entry and analysis with a significance level of p < 0.05. RESULT: The mean serum ferritin level was noticeably higher in uncontrolled T2DM patients as compared to controlled T2DM and control groups (p < 0.001). It was significantly correlated with HbA1c [r = 0.457, p < 0.001], fasting blood sugar (FBs) [r = 0.386, p < 0.001], serum iron [r = 0.430, p < 0.001], and systolic blood pressure (SBP) [r = 0.195, p = 0.047] in T2DM patients. A multivariate logistic regression model revealed that a rise in HbA1c (AOR = 3.67, 95% CI(1.50-8.98), serum iron (AOR = 1.02, 95% CI(1.01-1.04), male gender (AOR = 0.16, 95% CI(0.05-0.57) and being on oral hypoglycemic agent (OHA) monotherapy (AOR = 0.26, 95% CI(0.07-0.95) were key associated factors for the elevated serum ferritin among T2DM patients. CONCLUSION: The present study demonstrated that T2DM patients had elevated serum ferritin levels which might be related to the existence of long-term hyperglycaemia and that serum ferritin had a significant positive association with HbA1c and FBs, implying that it could be used as an additional biomarker to predict uncontrolled T2DM patients.