Efficacy and safety of bexagliflozin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: To assess the efficacy of bexagliflozin in reducing glycated haemoglobin (HbA1c) and the occurrence of side effects in patients with type 2 diabetes (T2DM). METHODS: We searched the PubMed, Embase, Cochrane and ClinicalTrials.gov databases for placebo-controlled, randomized clinical trials published up until 15 February 2023. The primary outcome was change in HbA1c. We computed weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: A total of six studies and 3111 patients were included, of whom 1951 were prescribed bexagliflozin. Compared with placebo, bexagliflozin significantly reduced HbA1c levels (WMD -0.53%; 95% CI -0.75, -0.31), fasting plasma glucose levels (WMD -1.45 mmol/L; 95% CI -2.32, -0.57), systolic blood pressure (WMD -4.66 mmHg; 95% CI -6.41, -2.92), diastolic blood pressure (WMD -2.12 mmHg; 95% CI -3.94, -0.30), body weight overall (WMD -1.61 kg; 95% CI -2.14, -1.07), and body weight in patients with a body mass index >25 kg/m2 (WMD -2.05 kg; 95% CI -2.78, -1.31). The proportion of patients who achieved HbA1c < 7% was higher in patients who received bexagliflozin as compared with placebo (OR 1.94; 95% CI 1.36-2.78). There were no significant differences between groups regarding side effects such as hypoglycaemia, genital mycotic infection, urinary tract infection, diarrhoea, headache, nausea, polyuria, diabetic ketoacidosis, or all-cause mortality. CONCLUSIONS: In this meta-analysis, the use of bexagliflozin was associated with improved clinical and laboratory measures in patients with T2DM compared with placebo, with a similar profile of side effects. These findings support the efficacy of bexagliflozin in the treatment of T2DM.

Efficacy and safety of carbohydrate counting versus other forms of dietary advice in patients with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised clinical trials.

BACKGROUND AND AIMS: Diabetes mellitus (DM) is one of the most prevalent chronic noncommunicable diseases globally, and the only way to reduce its complications is good glycaemic control. Insulin remains the only approved treatment for type 1 DM (T1DM) and is used by many with type 2 DM (T2DM). Carbohydrate counting is considered the ideal way to calculate meal-related insulin doses as it allows greater flexibility in diet and could, in some people, reduce the burden of the disease. The primary objective of this systematic review was to assess carbohydrate counting efficacy in reducing glycated haemoglobin (HbA1c ) levels and safety by not increasing hypoglycaemia risk, inducing an increase in body weight or blood lipids, or reducing the quality of life of people with T1DM. METHODS: We included randomised controlled clinical trials with a parallel-group design comparing any carbohydrate counting forms with standard care or other forms of dietary advice or insulin dose calculation in people with T1DM with a follow up period of at least 3 months and with no restrictions in language, age or settings. As a primary outcome, we consider the change of HbA1c levels within at least 3 months. Secondary outcomes were hypoglycaemia events, body weight changes, blood lipids levels, and the total daily insulin dose. We also evaluated health-related quality-of-life changes and questionnaires on satisfaction with treatment of diabetes. RESULTS: Data from 11 studies with 899 patients were retrieved with a mean follow-up of 52 ± 35.5 weeks. Carbohydrate counting is not better in reducing HbA1c levels (SMD-0.24%, 95% CI -0.68 to 0.21) than all dietary advice forms. However, this finding was highly heterogeneous. We identified three studies that account for most of the heterogeneity using clustering algorithms. A second analysis excluding these studies shows a meaningful reduction in HbA1c levels (SMD-0.52%, 95% CI -0.82 to -0.23) with low heterogeneity. In the subgroup analysis, carbohydrate counting significantly reduces HbA1c levels compared with usual diabetes education. Carbohydrate counting does not relate to any substantial change in blood lipids, body weight, hypoglycaemia risk or daily insulin dose. Finally, we analysed the effect of trial duration on reduction in HbA1c levels and found no significant change related to time. CONCLUSIONS: Carbohydrate counting is an efficacious technique to safely reduce the levels of HbA1c in adults and children compared with standard diabetes education, and its effect does not appear to change with prolonged time. Standardisation in reporting important outcomes such as hypoglycaemia and quality of life are vital to produce comparable evidence in carbohydrate counting clinical trials. This systematic review was registered in PROSPERO under code: CRD42020218499.

Effect of iron supplementation on HbA1c levels in pregnant women with and without anaemia.

BACKGROUND: Iron deficiency anaemia has been associated with higher HbA1c levels. However, during and after iron supplementation there is a decrease in HbA1c results, causing a misinterpretation. Our aim was to analyse the effect of iron supplementation on HbA1c levels in nondiabetic pregnant women with and without anaemia. METHODS: Pregnant women in prenatal care, without gestational diabetes (GDM) or previous diabetes mellitus (DM) that performed an oral glucose tolerance test (OGTT) in the third trimester of pregnancy were invited to participate. Clinical and laboratorial analyses were performed, including standardized questionnaire, OGTT, full blood count and HbA1c. RESULTS: A total of 231 pregnant women without DM or GDM were included in the study. According to anaemia and/or iron supplementation, we divided women in: no iron and no anaemia - Group 1 (N=86); no iron and with anaemia - Group 2 (N=29); iron and no anaemia - Group 3 (N=87); iron and anaemia - Group 4 (N=29). There was statistically a significant, although no clinically relevant, difference between HbA1c values in pregnant women in Groups 1 and 4 [5.1±0.4% (32±4.4mmol/mol) and 4.8±0.3% (29±3.3mmol/mol), P<0.01; respectively]. HbA1c values in pregnant women in Groups 1, 2 and 3 were similar, independently of anaemia [5.1±0.4% (32±4.4mmol/mol); 5.0±0.4% (31±4.4mmol/mol) and 5.0±0.4% (31±4.4mmol/mol); p>0.05; respectively]. CONCLUSIONS: Iron supplementation during pregnancy does not affect HbA1c levels and has no clinical impact in the final interpretation of results in the absence of anaemia or presence of mild anaemia. Interpreting HbA1c results in pregnant women during iron therapy and with moderate or severe anaemia still requires caution.

Factors associated with high levels of glycated haemoglobin in patients with type 1 diabetes: a multicentre study in Brazil.

OBJECTIVE: Long-term complications of type 1 diabetes mellitus (DM1) can be prevented with adequate glycaemic control. However, high levels of glycated haemoglobin (HbA1c) occur in 60%-90% of the patients with DM1. Thus, we aimed to investigate the role of sociodemographic, behavioural and clinical factors on the HbA1c levels of patients with DM1 in Brazil. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study was conducted in ambulatory patients with DM1 aged ≥18 years from 10 Brazilian cities. Sociodemographic, behavioural and clinical data were obtained through interviews. MAIN OUTCOME MEASURES: HbA1c level was measured by liquid chromatography. Hierarchical multiple variable linear regression models were used to identify factors correlated with high levels of HbA1c. RESULTS: Of 979 patients with DM1, 63.8% were women, and the mean age was 40 (SD 14.6) years. The mean HbA1c level was 9.4% (SD 2.2%), and 89.6% of the patients had HbA1c ≥7.0%. Factors independently correlated with increased HbA1c levels included: lower education, non-participation in diabetes classes/lecture during the year before, having a self-perception of poor adherence to diet and insulin, not having private medical care and not measuring the HbA1c levels in the prior year. Of note, poor adherence to diet and insulin were the independent factors most strongly associated with high levels of HbA1c (mean increment in HbA1c levels of 0.88% and 1.25%, respectively). CONCLUSION: Poor glycaemic control, which is common among Brazilian patients with DM1, is associated with lower education, self-perception of insufficient adherence to diet and insulin and inadequate monitoring of HbA1c levels. Specific actions, particularly those targeting improving adherence to diet and insulin, may contribute to successful management of patients with DM1.

Cross-sectional associations of impaired glucose metabolism measures with bleeding on probing and periodontitis.

AIM: This study assessed the associations of pre-diabetes and insulin resistance with bleeding on probing (BOP) and periodontitis among adults. MATERIALS AND METHODS: We included 1191 Hispanic adults aged 40-65 years, free of diabetes, enrolled in San Juan Overweight Adults Longitudinal Study. Pre-diabetes was defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired glycated haemoglobin. Impaired one-hour plasma glucose (1hPG) was defined as levels >155 mg/dl. Insulin resistance was defined using the study population-specific 75th percentile (HOMA-IR ≥ 3.13). High BOP was defined as percentage of teeth with bleeding ≥30%. Periodontitis was defined according to the CDC/AAP definition. RESULTS: After multivariable adjustment for age, gender, education, smoking status, alcohol consumption, physical activity, obesity, HDL-C, and plaque index, pre-diabetes with and without 1hPG, IFG, impaired 1hPG, IGT, and HOMA-IR were significantly associated with high BOP; pre-diabetes, IFG, and impaired 1hPG were significantly associated with severe periodontitis. Most of these associations remained significant when the analyses were restricted to non-smokers. CONCLUSIONS: This study suggests associations between pre-diabetes and insulin resistance with BOP and periodontitis. Given the high prevalence of impaired glucose metabolism and periodontitis, the assessment of the temporal sequence of these associations is of utmost importance.

Periodontal treatment and glycaemic control in patients with diabetes and periodontitis: an umbrella review.

BACKGROUND: Studies suggest that non-surgical periodontal treatment improves glycaemic control in patients with diabetes and periodontitis. The aim of this umbrella review is to summarize the effects of periodontal treatment on glycaemic control in patients with periodontitis and diabetes. METHODS: A systematic review of systematic reviews with or without meta-analysis published between 1995 and 2015 was performed. Three independent reviewers assessed for article selection, quality and data extraction. RESULTS: Thirteen (13) systematic reviews/meta-analysis were included for qualitative synthesis. A reduction (0.23 to 1.03 percentage points) in the levels of HbA1c at 3 months after periodontal intervention was found. This reduction was statistically significant in 10/12 meta-analysis. One review with sufficiently large samples found a non-significant reduction (-0.014 percentage points; 95% CI -0.18 to 0.16; p = 0.87). Only three studies separated the use of adjunctive antibiotics and found a reduction of 0.36 percentage points but the difference was not statistically significant. CONCLUSIONS: Highly heterogeneous short-term studies with small sample size suggest that periodontal treatment could help improve glycaemic control at 3 months in patients with type 2 diabetes and periodontitis. However, longer term studies having sufficient sample size do not provide evidence that periodontal therapy improves glycaemic control in these patients.

Antimicrobial photodynamic therapy as an alternative to systemic antibiotics: results from a double-blind, randomized, placebo-controlled, clinical study on type 2 diabetics.

AIM: This double-blind, placebo-controlled clinical study compared multiple applications of the antimicrobial photodynamic therapy (aPDT) treatment protocol, to systemic doxycycline as adjuvant to scaling and root planing (SRP) on type 2 diabetic patients on clinical, systemic and immune-inflammatory outcomes. MATERIALS AND METHODS: Thirty patients with Hba1c >7% were allocated in two groups, SRP + Doxy (n = 15) using systemic doxycycline 100 mg/day (14 days) and SRP + aPDT (n = 15) with multiple applications (0, 3, 7 and 14 days). Primary outcome was glycated haemoglobin levels (HbA1c). Clinical parameters: plaque score (PS), bleeding on probe, probing depth, suppuration, gingival recession, and clinical attachment level, percentage of pockets with desired clinical endpoint were measured at baseline and 3 months after therapy. Cytokine profile was assessed at 0, 1 and 3 month to measure IL1-ß, TNF-α and TGF-ß on gingival crevicular fluid. RESULTS: No significant difference was detected on HbA1c, between treatments. The SRP + aPDT group showed advantage on reducing moderate pockets in single-rooted teeth at 3 months. SRP + aPDT presented better results at 3 months on IL1-ß levels. There were no significant differences between TNF-α and TGF-ß. CONCLUSIONS: Both treatments improved clinical and systemic outcomes (Hba1c). SRP + aPDT performed better in moderate probing pocket depth on single-rooted teeth, reduced favourably inflammation in short term, and may be an alternative to systemic antibiotics. (Clinicaltrials.org ID NCT01595594).

Effect of iron deficiency anaemia on HbA1c levels is dependent on the degree of anaemia.

OBJECTIVES: Studies suggest that iron deficiency anaemia (IDA) is associated with higher HbA1c levels. We conducted a control­case study to investigate the effect of IDA on HbA1c levels, measured by two commonly used methods, in non-diabetic individuals. DESIGN AND METHODS: A total of 122 patients were included, 61 patients with IDA and 61 patients without anaemia. HbA1c was measured by both ion exchange HPLC Variant II Turbo BioRad and immunoturbidimetry (IT) Tina Quant II Roche Diagnostics in each sample. HbA1c results were compared between groups. For correlation analysis, patients were considered altogether. RESULTS: There was a significant difference between the results of HbA1c in patients with IDA [HPLC 5.6 ± 0.4% (38 ± 4.4 mmol/mol) and IT 5.7 ± 0.4% (39 ± 4.4 mmol/mol)] and those measured in patients without anaemia [HPLC 5.3 ± 0.4% (34 ± 4.4 mmol/mol) and IT 5.3 ± 0.3% (34 ± 3.3 mmol/mol)], (p < 0.001). Significant negative correlations were observed between total haemoglobin (Hb), haematocrit, mean corpuscular volume (MCV) and ferritin with HbA1c values measured by IT (r = − 0.557; r = − 0.539; r = − 0.488; r = − 0.499; p < 0.01; respectively). These negative correlations were weaker with HbA1c measured by HPLC (r = − 0.272; r = − 0.250; r = − 0.273; r = − 0.229 for Hb, haematocrit, MCV and ferritin; p < 0.05; respectively). HbA1c results were higher in patients with moderate and severe anaemia. However mild anaemia did not show significant effects on HbA1c results measured by both methods. CONCLUSIONS: IDA affects HbA1c results and this effect is dependent on anaemia degree. These upward changes are statistically significant but they may be not clinically relevant when the overall variability of the HbA1c test is considered. The presence of slight anaemia is likely to have a minor effect on HbA1c levels favouring its use to diagnose diabetes in patients with mild anaemia.

Reference values of glycosylated haemoglobin and fructosamin in dogs / Valores de referência da hemoglobina glicada e frutosamina em cães

Glycated haemoglobin and fructosamin levels are not commonly used to diagnosis Diabetes mellitus in dogs due to a lack of reference values. To estabilish the reference values and determination methods of glycated haemoglobin and frutosamine, both male and females, healthy dogs, 2-8 years old (n=100) were used. The methodologies used were the ionic resin and the kinetic method by the reduction of blue nitrotetrazolium, respectively. Medium values of glycated haemoglobin of 5.3-7.01% and 277.52-387. 30 for fructosamin established by Brazilian Diabetes Society methods can be adopted for dogs, both males and females.(AU)

A hemoglobina glicada e frutosamina são pouco utilizadas em cães para o diagnóstico do Diabetes mellitus devido à escassez e divergência de valores de referência. Com o objetivo de determinar os valores de referência e metodologia da hemoglobina glicada e frutosamina em cães, foram utilizados 100 cães sadios, machos e fêmeas, de dois a oito anos. As metodologias empregadas foram resina de troca iônica e método cinético por redução do azul de nitrotetrazólio, respectivamente. Os valores médios de hemoglobina glicada encontrados foram de 5,3-7,01% e de frutosamina de 277,52-387,3 ?molL-1, estabelecidos segundo metodologias da Sociedade Brasileira de Diabetes, e podem ser adotados para cães, machos e fêmeas.(AU)

Hemoglobina glicada no diagnóstico precoce de diabetes em amostra populacional de XangriLá, Brasil / Glycated hemoglobin in the early diagnosis of diabetes in a population sample from Xangri-Lá, Brazil

INTRODUÇÃO: Em 2010, a Associação Americana de Diabetes confirmou o uso da hemoglobina glicada (A1c) como exame diagnóstico de diabetes mellitus,com valores ™6,5%. A A1c é uma alternativa para o diagnóstico de pré-diabetes com limiar entre 6 a 6,4% para avaliar a prevalência de pré-diabetes e diabetes em pessoas assintomáticas. MÉTODOS: Este estudo transversal de base populacional usou a A1c e avaliou sua correlação com fatores de risco. Os participantes foram incluídos entre agosto/2012 e julho/2013. Os participantes residem no município de Xangri-Lá e têm entre 30 e 69 anos. As variáveis são: A1c, índice de massa corporal (IMC), idade, história familiar de diabetes e escolaridade. Coletou-se sangue, não exigindo jejum, para dosagem da A1c, utilizando-se a avaliação por cromatografia líquida de alta performance, de troca iônica: Variant II Turbo ­ BioRad. RESULTADOS: Incluímos 328 indivíduos, dos quais 31 têm A1c ™6,0%, resultando em uma prevalência de 9,5%. Os fatores de risco para A1c ™6% foram obesidade (IMC ™30 kg/m²), p = 0,001; idade ™50 anos, p = 0,04; presença de história familiar de diabetes, p = 0,01; e até cinco anos de estudo, p = 0,02. CONCLUSÃO: Demonstramos que a obesidade, na faixa etária do estudo, a idade a partir de 50 anos e a baixa escolaridade foram associadas com A1c ™6,0% e são compatíveis com indivíduos com pré-diabetes e diabetes assintomáticos no município de Xangri-Lá

INTRODUCTION: In 2010, the American Diabetes Association established the use of glycated hemoglobin (A1c) as a diagnostic test for diabetes mellitus (DM2), with values ™6.5%. A1c has been an alternative for the diagnosis of pre-diabetes, with a diagnostic threshold between 6% and 6.4% to evaluate the prevalence of pre-diabetes and diabetes among asymptomatic patients. METHODS: This population-based, cross-sectional study used A1c and evaluated the associated risk factors. Subjects were recruited between August 2012 and July 2013, lived in the municipality of Xangri-Lá, Brazil, and were between 30 and 69 years old. The analyzed variables were: A1c, body mass index (BMI), age, family history of diabetes, and educational attainment. Blood samples were collected for evaluation of A1c and did not require fasting. The samples were analyzed using the Variant II Turbo (BioRad), a high-performance liquid chromatography system with ionic exchange. RESULTS: Of the 328 subjects studied, 31 had A1c ™6.0%, resulting in a 9.5% prevalence. Risk factors for A1c values ™6.0% were obesity (BMI ™30 kg/m²), p=0.001; age ™50 years, p = 0.04; family history, p = 0.01; and having up to five years of study, p = 0.02. CONCLUSION: We demonstrate that obesity in the age group of the study, ages above 50 years, and low educational attainment were associated with A1c values ™6.0% and were compatible with asymptomatic diabetes mellitus and pre-diabetes mellitus in the municipality of Xangri-Lá

Reference values of glycosylated haemoglobin and fructosamin in dogs / Valores de referência da hemoglobina glicada e frutosamina em cães

Glycated haemoglobin and fructosamin levels are not commonly used to diagnosis Diabetes mellitus in dogs due to a lack of reference values. To estabilish the reference values and determination methods of glycated haemoglobin and frutosamine, both male and females, healthy dogs, 2-8 years old (n=100) were used. The methodologies used were the ionic resin and the kinetic method by the reduction of blue nitrotetrazolium, respectively. Medium values of glycated haemoglobin of 5.3-7.01% and 277.52-387. 30 for fructosamin established by Brazilian Diabetes Society methods can be adopted for dogs, both males and females.

A hemoglobina glicada e frutosamina são pouco utilizadas em cães para o diagnóstico do Diabetes mellitus devido à escassez e divergência de valores de referência. Com o objetivo de determinar os valores de referência e metodologia da hemoglobina glicada e frutosamina em cães, foram utilizados 100 cães sadios, machos e fêmeas, de dois a oito anos. As metodologias empregadas foram resina de troca iônica e método cinético por redução do azul de nitrotetrazólio, respectivamente. Os valores médios de hemoglobina glicada encontrados foram de 5,3-7,01% e de frutosamina de 277,52-387,3 ?molL-1, estabelecidos segundo metodologias da Sociedade Brasileira de Diabetes, e podem ser adotados para cães, machos e fêmeas.

Association between obesity and impaired glucose tolerance in new providence adolescents as demonstrated by the HbA1c test / Asociación entre la obesidad y los trastornos de tolerancia a la glucosa entre los adolescentes de nueva providencia según lo demostrado por la prueba de HbA1c

OBJECTIVE: To explore the association between obesity and the development of impaired glucose tolerance (IGT) in Bahamian adolescents. METHODS: Eight hundred and seventy-three adolescents were randomly selected from five high schools in New Providence. Each student's weight, height, and waist and hip circumferences were recorded to determine body mass index (BMI). Individuals with BMIs above the 84th and 95th percentiles were classified as overweight and obese, respectively. Venous blood samples were collected from each subject and haemoglobin Ai c (HbAi c) levels were measured using a direct immunoassay method. The criterion established by the International Expert Committee for the diagnosis of IGT (HbA i c concentration of 6.0-6.4%) was used. An analysis of covariance was performed to evaluate the relationship between obesity and IGT, and a logistic regression analysis predicted the risk of IGT based on BMI classification. RESULTS: Of the 861 adolescents who completed the study, 15.0% were classified as overweight, 15.2% as obese and 7.9% as severely obese. The overall cumulative prevalence of IGT based on HbAi c levels was 16 100 cases per 100 000 adolescents and was greater in males than in females. Higher percentages of overweight and obese students were identified as having IGT compared with their normal-weight counterparts. An analysis of covariance with post hoc analyses revealed that severely obese males and females, respectively were almost 26 (OR = 25.54, 95%CI 9.92, 65.77) or 23 (OR = 22.96, 95% CI 9.81, 53.73) times more likely to develop IGT than their normal-weight counterparts (p < 0.005). CONCLUSION: The data show a strong positive association between IGT and obesity among Bahamian adolescents.

OBJETIVO: Explorar la asociación entre la obesidad y el desarrollo de trastornos de tolerancia a la glucosa (IGT) en los adolescentes de Bahamas. MÉTODOS: Ochocientos setenta y tres adolescentes fueron seleccionados aleatoriamente de cinco escuelas secundarias en Nueva Providencia. Se registraron peso, altura, y las circunferencias de cintura y cadera de cada estudiante, para determinar el índice de masa corporal (IMC). Las personas con IMC por encima de los percentiles 84 y 95 fueron clasificados como con sobrepeso y obesos, respectivamente. Se obtuvieron muestras de sangre venosa de cada sujeto, y se midieron los niveles de hemoglobina A 1c (HbAc utilizando un método de inmunoensayo directo. Se utilizó el criterio establecido por el Comité Internacional de expertos para el diagnóstico de IGT (concentración de HbA 1c de 6.0-6.4%). Se realizó un análisis de covarianza para evaluar la relación entre la obesidad y IGT, y un análisis de regresión logística para predecir el riesgo de IGT sobre la base de la clasificación del IMC. RESULTADOS: De los 861 adolescentes que completaron el estudio, 15.0% fueron clasificados como con sobrepeso, 15.2% como obesos, y 7.9% como extremadamente obesos. La prevalencia acumulativa general de IGT basada en los niveles de HbA 1c fue 16 100 casos por 100 000 adolescentes, y fue mayor en los varones que en las mujeres. Mayores porcentajes de estudiantes con sobrepeso y obesidad fueron identificados con IGT en comparación con sus contrapartes de peso normal. Un análisis de covarianza con análisis post-hoc reveló que los varones y hembras extremadamente obesos, respectivamente, fueron casi 26 (OR = 25.54, 95%CI 9.92, 65.77) o 23 (OR = 22.96, 95% CI 9.81, 53.73) veces más propensas a desarrollar IGT que sus contrapartes de peso normal (p < 0.05). CONCLUSIÓN: Los datos muestran una fuerte asociación positiva entre IGT y obesidad entre los adolescentes de las Bahamas.