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Hemoglobin (Hb) is a hemeprotein found inside erythrocytes and is crucial in transporting oxygen and carbon dioxide in our bodies. In erythrocytes (Ery), the main energy source is glucose metabolized through glycolysis. However, a fraction of Hb can undergo glycation, in which a free amine group from the protein spontaneously binds to the carbonyl of glucose in the bloodstream, resulting in the formation of glycated hemoglobin (HbA1c), widely used as a marker for diabetes. Glycation leads to structural and conformational changes, compromising the function of proteins, and is intensified in the event of hyperglycemia. The main changes in Hb include structural alterations to the heme group, compromising its main function (oxygen transport). In addition, amyloid aggregates can form, which are strongly related to diabetic complications and neurodegenerative diseases. Therefore, this chapter discusses in vitro protocols for producing glycated Hb, as well as the main techniques and biophysical assays used to assess changes in the protein's structure before and after the glycation process. This more complete understanding of the effects of glycation on Hb is fundamental for understanding the complications associated with hyperglycemia and for developing more effective prevention and treatment strategies.

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BACKGROUND: Low adherence to the number of insulin injections and glycemic variability are among the challenges of insulin therapy in type 1 diabetes (T1D). The TOP1 study investigated the effect of switching from twice-daily (BID) basal insulin to once daily (OD) insulin glargine 300 U/mL (Gla-300) on glycemic control and quality of life. METHODS: In this 28-week, phase 4 trial, people with T1D aged ≥ 18 years, who were treated with BID basal insulin in combination with prandial rapid-acting insulin for at least 1 year, and had HbA1c between 7.5% and 10.0%, were switched to Gla-300 OD as basal insulin. The present study aimed to evaluate the impact of this change on HbA1c, glycemic profile, treatment satisfaction and safety. The change in HbA1c from baseline to Week 24 was the primary endpoint. RESULTS: One hundred and twenty-three people with T1D (mean age 37 ± 11 years; 54.5% female) were studied. The disease duration was 20.0 ± 9.8 years, baseline HbA1c and fasting plasma glucose (FPG) were 8.6 ± 0.7% and 201 ± 80.3 mg/dL, respectively. After switching from BID to OD insulin regimen, no significant change in HbA1c was observed from baseline to Week 24 (p = 0.873). There were significant reductions in fasting self-monitoring blood glucose (SMBG) from baseline to Week 24 (175 ± 42 vs. 156 ± 38 mg/dL; p < 0.0001), and in glycemic profile (8-point SMBG) at several time points. There was a significant decrease in the proportion of patients with at least one hypoglycemic event (p = 0.025), in numbers of hypoglycemic events per patient-years of any type (p = 0.036), symptomatic (p = 0.007), and confirmed ≤ 70 mg/dL events (p = 0.049) from run-in to the last 4 weeks on treatment. There were significant improvements in treatment satisfaction (p < 0.0001), perceived hyperglycemia (p < 0.0001) scores and satisfaction with the number of injections between post-run-in and Week 24, and a significant decrease in fear of hypoglycemia. CONCLUSIONS: Switch from BID basal insulin to OD Gla-300 as part of basal bolus therapy in T1D resulted in similar glycemic control as measured by HbA1c, but provided significant improvements in SMBG, daily glucose profile, a lower incidence of hypoglycemia and increased patient satisfaction. TRIAL REGISTRATION: NCT03406000.

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Type 2 diabetes mellitus (T2DM) is a major global health problem. Response to first-line therapy is variable. This is partially due to interindividual variability across those genes codifying transport, metabolising, and drug activation proteins involved in first-line pharmacological treatment. Single nucleotide polymorphisms (SNPs) of genes SLC22A1, SLC22A2 and SLC22A3 affect metformin therapeutic response in patients with T2DM patients. The present study investigated allelic and genotypic frequencies of organic cation (OCT)1, OCT2, and OCT3 polymorphisms among metformin-treated patients with type 2 diabetes mellitus (T2DM). It also reports the association between clinical and genetic variables with glycated haemoglobin (HbA1c) control in 59 patients with T2DM. Patients were genotyped through real-time PCR (TaqMan assays). Metformin plasmatic levels were determined by mass spectrometry. Neither the analysis of HbA1c control by SNPs in SLC22A1, SLC22A2 and SLC22A3, nor the dominant genotypic model analysis yielded statistical significance between genotypes in polymorphisms rs72552763 (P=0.467), rs622342 (P=0.221), rs316019 (P=0.220) and rs2076828 (P=0.215). HbA1c levels were different in rs72552763 [GAT/GAT, 6.0 (5.7-6.6), GAT/del=6.5 (6.2-9.0), del/del=6.5 (6.4-6.8); P=0.022] and rs622342 [A/A=6.0 (5.8-6.5), A/C=6.4 (6.1-7.7), C/C=6.8 (6.4-9.3); P=0.009] genotypes. The dominant genotypic model found the lowest HbA1c levels in GAT/GAT (P=0.005) and A/A (P=0.010), in rs72552763 (GAT/GAT vs. GAT/del + del/del) and rs622342 (A/A vs. A/C + CC), respectively. There was a significant correlation between HbA1c levels and metformin dosage amongst del allele carriers in rs72552763 (ß1=0.14, P<0.001, r2=0.387), as opposed to GAT/GAT in rs72552763. There were no differences between HbA1c values in the test set and those predicted by machine learning models employing a simple linear regression based on metformin dosage. Therefore, rs72552763 and rs622342 polymorphisms in SLC22A1 may affect metformin response determined by HbA1c levels in patients with T2DM. The del allele of SNP rs72552763 may serve as a metformin response biomarker.

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The treatment of Type 1 Diabetes Mellitus (T1DM) has always been a challenge for health professionals in relation to glycemic control. Increased body fat has been related to a worsening of the lipid profile and increased prevalence of dyslipidemia in this population, leading to negative repercussions on the control of cardiovascular risk. We aimed to investigate the distribution of lipid levels and the presence of dyslipidemia in children and adolescents with T1DM. A cross-sectional observational study was conducted with 81 individuals of both sexes (4-19 years) diagnosed with T1DM. Anthropometric and biochemical data were collected, in addition to data on physical activity level, sexual maturation stage, and insulin administration regimen. Lipid levels were categorized as normal, borderline, and elevated, and the presence of dyslipidemia was diagnosed by the presence of one or more altered lipid parameter. We noted a prevalence of dyslipidemia in 65.4% of the participants when considering borderline lipid values. Of those, 23.5% had one altered lipid level, and 42.0% had two or more. The main altered lipid levels were total cholesterol and triglycerides, followed by non-HDL-c. The main factor associated with the worsening of lipid levels was the increase in HbA1c. Sex had a significant effect on the levels of TC, HDL-c, and ApoA-I. The results of this study reinforce the need to monitor lipid profile in children and adolescents with T1DM, as well as the importance of early intervention in treating dyslipidemia, especially in patients with poor glycemic control.

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Latinos have high rates of type 2 diabetes mellitus (T2DM) yet are characterized as having health-promoting social networks. The impacts of COVID-19 on personal networks were complex, especially in urban areas with high proportion of immigrants such as the Bronx in NYC. Our objective was to test the extent to which network characteristics increase vulnerability or resiliency for glycemic control based on data gathered from Mexican-origin Bronx dwellers. We used two-wave panel study analyzing self-reported personal social networks (n=30participants; 600network members) and HbA1c levels via dried blood spots in 2019, before the COVID-19 pandemic, and in 2021, a time after initial lockdowns and when the pandemic was still ravaging the community of study. Regression models adjusted for individual-level variables including sociodemographic and health indicators (i.e., physical health including COVID-19 and mental health). We found that an increase in the proportion of network members with diabetes predicted an increase in participant's HbA1c levels from 2019 to 2021 (ß=0.044, p < 0.05). Also, a greater proportion of network members consuming "an American diet" in 2019 predicted a decrease in participant's HbA1c levels (ß=-0.028, p < 0.01), while a greater proportion of network members that encouraged participants' health in 2019 predicted an increase in participant's HbA1c levels (ß=0.033, p < 0.05). Our study sheds light on specific social network characteristics relevant to individual diabetes outcomes, including potential longitudinal mechanistic effects that played out at the peak of the COVID-19 crisis.

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SUMMARY OBJECTIVE: Obesity is a chronic multisystem disease associated with increased morbidity and mortality. Obesity, which is a complex, multifactorial, and heterogeneous condition, is thought to result from the interaction of environmental, physiological, and genetic factors. In this study, the relationship between serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB in obese and healthy cohorts was evaluated along with biochemical and gene expressions and with demographic and clinical covariates, and their effects on obesity were evaluated. METHODS: This case-control study included a total of 80 individuals, 40 healthy controls and 40 obesity patients, consisting of female and male aged between 18 and 63 years. Hemoglobin A1c, mucin-1, and nuclear factor κB levels were determined by ELISA in serum samples obtained from patients. In addition, aspartate aminotransferase, alanine transaminase, low density lipoprotein, and glucose values were measured. The gene expressions of the same markers were analyzed by quantitative real-time polymerase chain reaction, and their regulation status was defined. RESULTS: Serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB were found to be high in obese individuals (p<0.05). The gene expression of these serum markers was found to be upregulated. Of the anthropometric measurements, waist circumference and body mass index were correlated with both serum markers and gene expressions (p<0.05). CONCLUSION: In addition to the known association of hemoglobin A1c and nuclear factor κB with obesity, serum levels of mucin-1 as well as upregulation of genes point to its modifier effect on obesity. These parameters can be the powerful markers in the diagnosis of obesity.

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The national burden of HCV has significantly mounted over the period of last few decades placing Pakistan at the worst placement of second largest burden of HCV globally. Herein for the first time from Pakistan, we examined clinical correlation of potential biomarkers with HCV. Nation-wide study was conducted on 13,348 suspected HCV patients during 2018-2022. During pre-COVID-19 era of 2018-2019, prevalence of HCV remained 30%. During 2018, among HCV positive patients, 91% of ALT, 63% of AST, 67% of GGT, 28% of Bili T, 62% of HB, 15% of HBA1C, 25% of CREAT, 15% of PT, 15% of aPTT and 64% of AFP were abnormal. During 2019, among HCV infected 74.47% of ALT, 63.54% of AST, 70.24% of GGT, 24.71% of Bili T, 8.77% of HB and 75% of AFP were raised. CT/CAT scan revealed 4.65% liver complications (mild 13.04%, moderate 30.43% and severe 56.52%). During 2020, HCV prevalence remained 25%. 65.17% of ALT, 64.20% of AST, 68.75% of GGT, 31.25% of Bili T, 20.97% of HB, 4.65% of CREAT and 73.68% of AFP levels were raised. CAT analysis revealed liver complications among 4.41% (14.81% mild, 40.74% moderate, and 44.44% sever). 85.71% of participants diabetes was out of control. During 2021, HCV prevalence remained 27.1%. ALT (73.86%), AST (50.6%), GGT (67.95%), Bili T (28.21%), HB (20%), CREAT (5.8%) and AFP (82.14%) levels were abnormal. During 2022, the levels of ALT (56.06%), AST (56.36%), GGT (56.6%), Bili T (19.23%), HB (43.48%), HBA1C (14.81), CREAT (18.92%), AFP (93.75%) were abnormal. CAT analysis revealed 7.46% liver complications (25% mild, 30.36% moderate, and 42.86% sever). During 2021-2022, 83.33% of subject's diabetes was not controlled.

A carga nacional de HCV aumentou significativamente ao longo das últimas décadas, colocando o Paquistão na pior colocação da segunda maior carga de HCV globalmente. Pela primeira vez no Paquistão, examinamos a correlação clínica de potenciais biomarcadores com HCV. Um estudo nacional foi realizado com 13.348 pacientes suspeitos de HCV de 2018 a 2022. Durante a era pré-COVID-19 de 2018 a 2019, a prevalência do HCV permaneceu em 30%. Durante 2018, entre pacientes positivos para HCV, 91% de ALT, 63% de AST, 67% de GGT, 28% de Bili T, 62% de HB, 15% de HBA1C, 25% de CREAT, 15% de PT, 15% de aPTT e 64% de AFP eram anormais. Durante 2019, entre os infectados pelo HCV, 74,47% de ALT, 63,54% de AST, 70,24% de GGT, 24,71% de Bili T, 8,77% de HB e 75% de AFP foram elevados. A TC/TAC revelou 4,65% de complicações hepáticas (leve 13,04%, moderada 30,43% e grave 56,52%). Durante 2020, a prevalência do HCV permaneceu em 25%. 65,17% de ALT, 64,20% de AST, 68,75% de GGT, 31,25% de Bili T, 20,97% de HB, 4,65% de CREAT e 73,68% de AFP estavam elevados. A análise de TAC revelou complicações hepáticas em 4,41% (14,81% leves, 40,74% moderadas e 44,44% graves). 85,71% dos participantes o diabetes estava fora de controle. Durante 2021, a prevalência de HCV permaneceu em 27,1%. Os níveis de ALT (73,86%), AST (50,6%), GGT (67,95%), Bili T (28,21%), HB (20%), CREAT (5,8%) e AFP (82,14%) estavam anormais. Durante 2022, os níveis de ALT (56,06%), AST (56,36%), GGT (56,6%), Bili T (19,23%), HB (43,48%), HBA1C (14,81), CREAT (18,92%), AFP (93,75%) eram anormais. A análise de TAC revelou 7,46% de complicações hepáticas (25% leves, 30,36% moderadas e 42,86% severas). Durante 2021 e 2022, 83,33% do diabetes do sujeito não foi controlado.

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On March 11, 2020, the World Health Organization (WHO) declared a new coronavirus infection caused by the SARS-CoV-2 virus as a pandemic, making it the 11th pandemic of the 20th and 21st centuries. This study investigated the clinical and laboratory results (D-dimer, conventional coagulation, and HbA1c biomarker concentrations) of 150 patients (75 male and 75 female) with confirmed COVID-19 pneumonia and 50 controls (25 male and 25 female). For disease diagnosis, all COVID-19 patients were given a Real-Time Reverse Transcription Polymerase Chain Reaction Assay (RT-PCR). The findings revealed that D-dimer and HbA1c levels in COVID-19 patients were significantly higher (P 0.001) at the time of admission; In COVID-19 patients, there was also a strong correlation between D-dimer levels and HbA1c levels (P 0.001). In conclusion, COVID-19 patients are more likely to have a poor prognosis if their D-dimer and HbA1c levels remain uncontrolled over a lengthy period. To lower the likelihood of a bad prognosis in COVID-19, patients with higher levels of D-dimer and HbA1c should be continuously monitored.

Em 11 de março de 2020, a Organização Mundial da Saúde (OMS) declarou uma nova infecção por coronavírus causada pelo vírus SARS-CoV-2 como uma pandemia, tornando-a a 11ª pandemia dos séculos XX e XXI. Este estudo investigou os resultados clínicos e laboratoriais (D-dímero, coagulação convencional e concentrações de biomarcadores HbA1c) de 150 pacientes (75 homens e 75 mulheres) com pneumonia por COVID-19 confirmada e 50 controles (25 homens e 25 mulheres). Para o diagnóstico da doença, todos os pacientes com COVID-19 receberam um Ensaio de Reação em Cadeia da Polimerase com Transcrição Reversa em Tempo Real (RT-PCR). Os achados revelaram que os níveis de D-dímero e HbA1c em pacientes com COVID-19 foram significativamente maiores (P 0,001) no momento da admissão. Em pacientes com COVID-19, também houve uma forte correlação entre os níveis de D-dímero e os níveis de HbA1c (P 0,001). Em conclusão, os pacientes com COVID-19 têm maior probabilidade de ter um prognóstico ruim se seus níveis de D-dímero e HbA1c permanecerem descontrolados por um longo período. Para diminuir a probabilidade de um mau prognóstico na COVID-19, os pacientes com níveis mais altos de D-dímero e HbA1c devem ser monitorados continuamente.

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Intermittent fasting (IF) regimens have emerged as a dietary tool to improve the glycemic profile, but a critical appraisal of clinical studies assessing the effects of IF regimens in patients with diabetes is needed. Thus, this review encompasses clinical studies examining the impact of different IF regimens on markers of glycemic control in patients with diabetes. Furthermore, clinical nuances relative to pharmacological treatment are also addressed, mainly insulin therapy, to discuss the risk of hypoglycemic events. Only a handful of clinical studies have investigated the effects of IF on patients with diabetes. Overall, IF regimens may elicit modest benefits on glycemic parameters in patients with diabetes, but their effects are not necessarily greater than those of control diets. Last, although IF regimens may be considered safe for patients receiving insulin therapy within interventional and observational research, markers of glycemic control must be constantly monitored in clinical practice to reduce the risk of hypoglycemia and its related complications.

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Introducción: el Finnish Diabetes Risk Score (FINDRISC) mostró alta sensibilidad y especificidad para la detección de personas que evolucionarían a diabetes mellitus (DM) en las poblaciones estudiadas, por lo cual se decidió utilizarlo entre quienes concurrieron por diferentes motivos a realizarse análisis de laboratorio en centros de la Asociación de Laboratorios de Alta Complejidad (ALAC), con el objeto de identificar personas con diferentes niveles de riesgo de presentar alteraciones de la glucemia en ayunas (GA) y de la HbA1c. Objetivos: explorar la asociación entre la puntuación del FINDRISC con GA y HbA1c, estableciendo el punto de corte de mayor sensibilidad y especificidad para encontrar una GA ≥100 mg/dL y una HbA1c ≥5,7% (38,8 mmol/mol), en una población que concurrió a centros de la ALAC. Materiales y métodos: se incluyeron 1.175 individuos de 45 laboratorios de la ALAC, procesamiento local de glucemia y centralizado de HbA1c (high performance liquid chromatography, HPLC). Análisis estadístico: chi-cuadrado, Odds Ratio, ANOVA, test de Tukey, regresión logística binomial y curvas ROC. Resultados: los puntajes totales del FINDRISC se asociaron de manera positiva y estadísticamente significativa, tanto con los valores de GA como con los niveles de HbA1c. Entre sus variables, una edad mayor o igual a 45 años, un perímetro abdominal de alto riesgo, un índice de masa corporal mayor o igual a 25 Kg/m., la presencia de antecedentes familiares de DM (padres, hermanos o hijos) y la existencia de antecedentes de medicación antihipertensiva se asociaron de manera significativa con valores de GA iguales o superiores a 100 mg/dL y/o niveles de HbA1c iguales o mayores a 5,7% (38,8 mmol/mol). No se halló asociación significativa con la realización de actividad física (al menos 30 minutos diarios) ni con el registro de ingesta diario de frutas y verduras. Los valores medios de GA y HbA1c en individuos con puntajes totales del FINDRISC menores o iguales a 11 fueron de 89,9 mg/dL y 5,2% (33,0 mmol/mol), respectivamente, elevándose hasta valores medios de 116,1 mg/dL y 6,1% (43,0 mmol/mol) en los individuos con puntajes iguales o superiores a 21, siguiendo una asociación del tipo "dosis/respuesta". Por curvas ROC, un FINDRISC de 13 presenta una sensibilidad del 81,89%, especificidad del 67,60% y 70,55% de diagnósticos correctos de HbA1c ≥5,7% (38,8 mmol/mol), y una sensibilidad del 72,50%, especificidad del 70,62% y 71,20% de diagnósticos correctos para encontrar personas con una GA ≥100 mg/dL. Conclusiones: el puntaje del FINDRISC se relacionó con niveles crecientes de GA y HbA1c, resultando útil para encontrar personas con GA ≥100 mg/dL y HbA1c ≥5,7% (38,8 mmol/mol) en la población estudiada.

Introduction: the Finnish Diabetes Risk Score (FINDRISC) has high sensitivity and specificity for the identification of people at risk of diabetes mellitus (DM) in various populations. Therefore, we aimed to use this index to identify individuals at risk of having alterations in fasting glycemia (FG) and HbA1c among those who underwent laboratory analysis at ALAC, Argentina. Objectives: to explore the relationships of the FINDRISC score with the fasting blood glucose (FG) concentration and glycated hemoglobin (HbA1c) level, and to establish appropriate cut-off scores to predict FG ≥100 mg/dL and HbA1c ≥5.7% (38.8 mmol/mol) in this population. Materials and methods: we recruited 1,175 individuals from 45 ALAC laboratories for whom FG and HbA1c had been measured. We analyzed the data using the chi square test, odds ratios, ANOVA plus Tukey's post-hoc test, binomial logistic regression, and receiver operating characteristic (ROC) curves. Results: total FINDRISC score significantly positively correlated with both FG and HbA1c. Of the constituent variables, age ≥45 years, a large waist circumference, a body mass index ≥25 kg/m., a close family history of DM, and the use of antihypertensive medication were significantly associated with FG ≥100 mg/dL and/or HbA1c ≥5.7% (38.8 mmol/mol). However, no significant association was found with physical activity or the daily consumption of fruit and vegetables. The mean FG and HbA1c for individuals with total FINDRISC scores ≤11 were 89.9 mg/dL and 5.2% (33.0 mmol/mol), respectively, which increased to 116.1 mg/dL and 6.1% (43.0 mmol/mol) for individuals with scores ≥21, with a dose/response-type relationship. ROC analysis showed that a FINDRISC of 13 was associated with a sensitivity of 81.89%, a specificity of 67.60%, and a correct diagnosis rate of 70.55% for HbA1c ≥5.7% (38.8 mmol/mol); and a sensitivity of 72.50%, a specificity of 70.62%, and a correct diagnosis rate of 71.20% for FG ≥100 mg/dL. Conclusions: FINDRISC score increases with increasing FG and HbA1c, and is a useful means of identifying people with FG ≥100 mg/dL and HbA1c ≥5.7% (38.8 mmol/mol).

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INTRODUCTION: Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. OBJECTIVE: The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. METHODS: The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). RESULTS: There was a strong positive correlation between fructosamine and HbA1c (n = 318, r = 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r = 0.61, p < 0.001) or using glucocorticoids (n = 96, r = 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r = 0.66, p < 0.001), hypoproteinemia (n = 54, r = 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r = 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r = 0.54, p = 0.001) and with reduced eGFR (n = 67, r = 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r = 0.49, p < 0.001; n = 111, r = 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. CONCLUSIONS: Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy.

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Type 1 diabetes mellitus (T1DM) is one of the major chronic diseases in children worldwide. This study aimed to investigate interleukin-10 (IL-10) gene expression and tumor necrosis factor-alpha (TNF-α) in T1DM. A total of 107 patients were included, 15 were T1DM in ketoacidosis, 30 patients had T1DM and HbA1c ≥ 8%; 32 patients had T1DM and presented HbA1c < 8%; and 30 were controls. The expression of peripheral blood mononuclear cells was performed using the reverse transcriptase-polymerase chain reaction in real time. The cytokines gene expression was higher in patients with T1DM. The IL-10 gene expression increased substantially in patients with ketoacidosis, and there was a positive correlation with HbA1c. A negative correlation was found for IL-10 expression and the age of patients with diabetes, and the time of diagnosis of the disease. There was a positive correlation between TNF-α expression with age. The expression of IL-10 and TNF-α genes showed a significant increase in DM1 patients. Once current T1DM treatment is based on exogenous insulin, there is a need for other therapies, and inflammatory biomarkers could bring new possibilities to the therapeutic approach of the patients.

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BACKGROUND: Periodontitis worsens the hyperglycaemia in patients with type 2 diabetes mellitus (T2DM). Subgingival instrumentation, with or without surgical access, is the gold-standard treatment for periodontitis. The aim was to summarize the evidence on the effect of subgingival instrumentation (with or without open flap) on the reduction of glycosylated haemoglobin (HbA1c). METHODS: Nine electronic databases were searched up to 15 February 2023. Twelve randomized controlled trials with at least 6 months of follow-up were included. Studies using systemic or local-delivery antimicrobial therapies were excluded. Meta-analyses were performed using the random-effects model. The sources of heterogeneity were assessed by applying linear meta-regression. Risk of bias was assessed by RoB 2, and certainty of evidence by GRADE. RESULTS: Eleven studies were included in the quantitative analyses (1374 patients). Subgingival instrumentation resulted in 0.29% lower HbA1c (95% confidence interval: 0.10-0.47; p = .03) compared with non-active treatment. DISCUSSION: None of the 12 studies were assessed as having low risk of bias. The percentage of females and the time of diabetes diagnosis significantly explained the high level of heterogeneity. Subgingival periodontal therapy results in a significant and clinically relevant improvement in glycaemic control over 6 months in patients with T2DM and periodontitis. The grade of evidence was moderate.

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Background: A sedentary lifestyle and an unhealthy diet have considerably increased the incidence of diabetes mellitus worldwide in recent decades, which has generated a high rate of associated chronic complications. Methods: A narrative review was performed in MEDLINE, EMBASES and SciELO databases, including 162 articles. Results: Diabetic neuropathy (DN) is the most common of these complications, mainly producing two types of involvement: sensorimotor neuropathy, whose most common form is symmetric distal polyneuropathy, and autonomic neuropathies, affecting the cardiovascular, gastrointestinal, and urogenital system. Although hyperglycemia is the main metabolic alteration involved in its genesis, the presents of obesity, dyslipidemia, arterial hypertension, and smoking, play an additional role in its appearance. In the pathophysiology, three main phenomena stand out: oxidative stress, the formation of advanced glycosylation end-products, and microvasculature damage. Diagnosis is clinical, and it is recommended to use a 10 g monofilament and a 128 Hz tuning fork as screening tools. Glycemic control and non-pharmacological interventions constitute the mainstay of DN treatment, although there are currently investigations in antioxidant therapies, in addition to pain management. Conclusions: Diabetes mellitus causes damage to peripheral nerves, being the most common form of this, distal symmetric polyneuropathy. Control of glycemia and comorbidities contribute to prevent, postpone, and reduce its severity. Pharmacological interventions are intended to relieve pain.

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The association of diabetes with increased large artery stiffness is not definitively established. We aimed to describe the carotid-femoral pulse wave velocity (cf-PWV) in participants with and without diabetes and whether the cf-PWV could vary among the different laboratory-based criteria used. A cross-sectional analysis using baseline data from 13,912 adults was used. cf-PWV as well as anthropometric, biochemical, and clinical data were measured. Diabetes was defined by previous medical diagnosis, medication use, fasting glucose, an oral glucose tolerance test (GTT), or glycated hemoglobin (HbA1c). The prevalence of diabetes was 18.7%, higher in men than in women. After adjustment, participants with diabetes showed higher cf-PWV (men: 9.7 ± 1.7 vs 9.4 ± 1.7 m/s, P < .05; women: 9.4 ± 1.6 vs 9.1 ± 1.7 m/s, P < .05). We observed a progressive increase in cf-PWV as >1 laboratory-based criterion for diabetes diagnosis was reached. Also, participants with diabetes with alterations in any laboratory-based criteria had higher cf-PWV than participants without diabetes, regardless of sex. In summary, diabetes is associated with higher cf-PWV as is each laboratory-based parameter used for its diagnosis. These results support the strong consequences of glucose dysregulation on the vascular system and provide evidence to screen all parameters involved in glycemic metabolism to improve vascular health.

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OBJECTIVE: This study aimed to assess the longitudinal predictions between glycated hemoglobin A1c (HbA1c) and physical performance scores in different epidemiological contexts of aging. MATERIAL AND METHODS: Longitudinal data of 1,337 older people from three countries (Canada, Brazil and Colombia) of the International Mobility in Aging Study (IMIAS) were used to assess the relationship between HbA1c and Short Physical Performance Battery (SPPB) scores between 2012 and 2016. Linear Mixed Models grouped by sex and adjusted by Age, Study site, Chronic Conditions, Anthropometric Measures, and Inflammatory Level were used to estimate the influence of HbA1c and covariates on SPPB scores. RESULTS: At the IMIAS baseline, Latin American (LA) cities had higher HbA1c averages compared to Canadian cities, with Natal (Brazil) being the city with the highest HbA1c averages in men and women (6.32 ± 1.49; 6,56 ± 1.70 respectively). SPPB scores were significantly lower in LA cities, and older people in Natal had lower SPPB averages in men (9.67 ± 2.38; p-value < 0.05) and women (8.52 ± 2.33; p-value <0.05). In the multivariate mixed linear models of longitudinal analyses, HbA1c was significantly associated with lower SPPB scores in men (ß = -0.25, 95% CI: -0.39 to -0.12, p-value = 0.02) but not in women. CONCLUSION: High HbA1c levels at baseline were longitudinally associated in older adults from different countries, and this association was observed only in men and not in women. This study highlights a possible influence of gender on this relationship.

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Leptin and interleukin-1 beta (IL-1β) are two extensively studied biomarkers associated with metabolic syndrome (MetS) and osteoarthritis (OA). Previous studies have mostly focused on either MetS or OA alone, with no available data on Vietnamese patients. This study aimed to investigate the levels of leptin and IL-1β in this patient population and explore their association with clinical parameters of MetS and OA. The study included 164 patients with primary knee OA, who were classified into two categories based on the presence of MetS, and 78 healthy controls. The plasma leptin and IL-1β levels were quantified by ELISA and correlated with clinical parameters. Leptin levels were higher in patients with OA (11.50±10.04 ng/mL) than in healthy controls (0.54±0.37 ng/mL) and increased in patients with MetS compared to those without MetS. IL-1β levels were also significantly higher in OA patients (14.63±15.87 pg/mL) than in controls (7.79±5.11 pg/mL), but were not significantly different between the MetS and non-MetS groups. Leptin levels were positively correlated with body mass index, waist-to-hip ratio, visual analogue scale scores, HbA1c and insulin levels, and HOMA-IR index, whereas IL-1β levels were only correlated with insulin levels and HOMA-IR index. ROC curve analysis revealed that leptin and IL-1β levels could distinguish individuals with and without OA (AUC=0.96; 0.88, respectively), and individuals with and without MetS (AUC=0.82; 0.71, respectively). Our findings suggested that both leptin and IL-1β levels were associated with both MetS and OA and may play a critical role in the pathogenesis of MetS-related OA.

RESUMO

Abstract Introduction Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. Objective The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. Methods The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). Results There was a strong positive correlation between fructosamine and HbA1c (n = 318, r= 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r= 0.61, p < 0.001) or using glucocorticoids (n = 96, r= 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r= 0.66, p < 0.001), hypoproteinemia (n = 54, r= 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r= 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r= 0.54, p = 0.001) and with reduced eGFR (n = 67, r= 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r= 0.49, p < 0.001; n = 111, r= 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. Conclusions Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy.

RESUMO

Abstract BACKGROUND: Chronically elevated alpha-2-macroglobulin (A2MG) in the blood has been correlated with diabetes and the HbA1c profile; however, no systematic review has been conducted to evaluate the association of A2MG salivary levels and glycemia or HbA1c levels in diabetes mellitus type 2 (DM2) patients. OBJECTIVE: To evaluate whether A2MG salivary levels are related to the glycemia or HbA1c levels in DM2 patients. DESIGN AND SETTING: Systematic review developed at Universidade Federal de Uberlândia (UFU), Brazil. METHODS: Eight databases were used as research sources. The eligibility criteria included studies that reported data regarding mean salivary A2MG and the correlation between glycemia and/or HbA1c levels of DM2 subjects (uncontrolled and well-controlled) and non-diabetic subjects. The risk of bias of the studies selected was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools for use in JBI systematic reviews. Pooled correlation coefficients were estimated using the Hunter-Schmidt method. Study estimates were weighted according to their sample size, and heterogeneity was calculated using the chi-square statistic. RESULTS: Four studies on DM2 patients were included in this systematic review after careful analysis of 1482 studies. Three studies compared A2MG with HbA1c and glycemia. Overall, the correlation between A2MG and HbA1c was strong (r = 0.838). In contrast, the correlation between A2MG and glycemia was low (r = 0.354). CONCLUSION: The strong association between HbA1C and salivary A2MG suggests that this salivary protein has the potential to be a surrogate for HbA1C, if corroboratory further evidence is obtained through large-scale studies.

RESUMO

ABSTRACT Objective: The aim of this study was to investigate the factors associated with hypoglycemia and severe hypoglycemia (SH) in individuals with type 1 diabetes mellitus (T1D) in Brazil. Materials and methods: This multicenter, cross-sectional study was conducted between August 2011 and August 2014 across 10 Brazilian cities. The data were obtained from 1,760 individuals with T1D. Sociodemographic and clinical characteristics related to hypoglycemic events in the previous 4 weeks were evaluated. Results: Of 1,760 individuals evaluated, 1,319 (74.9%) reported at least one episode of hypoglycemia in the previous 4 weeks. The main factors associated with hypoglycemia were lower hemoglobin A1c (HbA1c) level, better adherence to self-monitoring of blood glucose (SMBG), and higher education level. Episodes of SH were reported by 251 (19%) individuals who, compared with subjects with nonsevere hypoglycemia, received lower doses of prandial insulin and higher doses of basal insulin, in addition to reporting less frequent use of long-acting basal insulin analogs. The percentage of SH episodes was evenly distributed across all ranges of HbA1c levels, and there were no correlations between the mean number of nonsevere or severe hypoglycemic events and HbA1c values. Higher alcohol consumption and more frequent hospitalizations were independently associated with SH. Conclusion: Although individuals presenting with hypoglycemia had lower HbA1c values than those not presenting hypoglycemia, there were no correlations between the number of nonsevere hypoglycemia or SH and HbA1c values. Also, the frequency of SH was evenly distributed across all ranges of HbA1c values. Better adherence to SMBG and higher education level were associated with hypoglycemia, while alcohol consumption, higher doses of basal insulin, and more frequent hospitalizations in the previous year were associated with SH.