DNA methylation reprogramming mediates transgenerational diabetogenic effect induced by early-life p,p'-DDE exposure.

Increasing evidence shows that an adverse environment during the early fetal development can affect the epigenetic modifications on a wide range of diabetes-related genes, leading to an increased diabetic susceptibility in adulthood or even in subsequent generations. p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) is a break-down product of the pesticide dichlorodiphenyltrichloroethane (DDT). p,p'-DDE has been associated with various health concerns, such as diabetogenic effect. However, the precise molecular mechanism remains unclear. In this study, p,p'-DDE was given by gavage to pregnant rat dams from gestational day (GD) 8 to GD15 to generate male germline to investiagate the transgenerational effects. We found that early-life p,p'-DDE exposure increased the transgenerational diabetic susceptibility through male germline inheritance. In utero exposure to p,p'-DDE altered the sperm DNA methylome in F1 progeny, and a significant number of those differentially methylated genes could be inherited by F2 progeny. Furthermore, early-life p,p'-DDE exposure altered DNA methylation in glucose metabolic genes Gck and G6pc in sperm and the methylation modification were also found in liver of the next generation. Our study demonstrate that DNA methylation plays a critical role in mediating transgenerational diabetogenic effect induced by early-life p,p'-DDE exposure.

Differences in the diabetogenic effect of statins in patients with prediabetes. The PRELIPID study / Diferencias en cuanto al efecto diabetógeno de las estatinas en pacientes con prediabetes. Estudio Prelipid

Introduction:Statins are used with the understanding that a slightly increased risk of diabetes is outweighed by their cardiovascular benefits. However, it may be necessary to reconsider whether statin therapy really increase this risk mainly in the population with prediabetes.Methods:A multicenter, cross-sectional, observational study was conducted to assess the relationship between statin therapy and glucose metabolism in 407 patients aged 63.1 years (11SD) diagnosed with dyslipidemia and prediabetes treated in specialized lipid clinics in Spain.Results:Significant differences were found in HbA1c values among treatment groups (p=0.015). Patients treated with pitavastatin (1–4mg/day) showed the lowest HbA1c levels, with significant differences compared to patients treated with atorvastatin 40–80mg/day (p=0.016) and simvastatin 10–40mg/day (p=0.036). By contrast, patients treated with atorvastatin 40–80mg/day showed the highest HbA1c levels compared to those receiving atorvastatin 10–20mg/day (p=0.003), pitavastatin 1–4mg/day (p=0.016), pravastatin 20–40mg/day (p=0.027), rosuvastatin 5–10mg/day (p=0.043), and no statin treatment (p=0.004). Patients treated with simvastatin 10–40mg/day also had higher values than those treated with atorvastatin 10–20mg/day (p=0.016) and pitavastatin 1–4mg/day (p=0.036) or with no statin treatment (p=0.018).Conclusions:This study suggests that there are differences in the diabetogenic effect of statins. Simvastatin and high doses of atorvastatin may be associated with greater impairment in glucose metabolism than pitavastatin and other statins with less lipid-lowering potency such as pravastatin. (AU)

Introducción:Las estatinas son utilizadas de acuerdo con el entendimiento de que el pequeño riesgo de incremento de diabetes se ve compensado por sus beneficios cardiovasculares. Sin embargo, puede resultar necesario reconsiderar si la terapia con estatinas incrementa realmente el riesgo, principalmente en la población con prediabetes.Métodos:Se realizó un estudio multicéntrico, transversal y observacional para evaluar la relación entre la terapia con estatinas y el metabolismo de la glucosa en 407 pacientes de 63,1 años (11 DE) diagnosticados de dislipidemia y prediabetes tratados en clínicas especializadas en lípidos en España.Resultados:Se encontraron diferencias significativas en los valores de HbA1c entre los grupos de tratamiento (p=0,015). Los pacientes tratados con pitavastatina (1-4mg/día) reflejaron los menores niveles de HbA1c, con diferencias significativas en comparación con los pacientes tratados con atorvastatina 40-80mg/día (p=0,016) y simvastatina 10-40mg/día (p=0,036). Por contra, los pacientes tratados con atorvastatina 40-80mg/día reflejaron los mayores niveles de HbA1c en comparación con los pacientes que recibieron atorvastatina 10-20mg/día (p=0,003), pitavastatina 1-4mg/día (p=0,016), pravastatina 20-40mg/día (p=0,027), rosuvastatina 5-10mg/día (p=0,043) y los que no recibieron estatinas (p=0,004). Los pacientes tratados con simvastatina 10-40mg/día tuvieron también valores más elevados que aquellos pacientes tratados con atorvastatina 10-20mg/día (p=0,016) y pitavastatina 1-4mg/día (p=0,036) que no recibieron estatinas (p=0,018).Conclusiones:El presente estudio sugiere que existen diferencias en cuanto al efecto diabetógeno de las estatinas. Simvastatina y las altas dosis de atorvastatina pueden guardar relación con un mayor deterioro del metabolismo de la glucosa que pitavastatina y demás estatinas con menor potencia de reducción de lípidos, tales como pravastatina. (AU)

Differences in the diabetogenic effect of statins in patients with prediabetes. The PRELIPID study.

INTRODUCTION: Statins are used with the understanding that a slightly increased risk of diabetes is outweighed by their cardiovascular benefits. However, it may be necessary to reconsider whether statin therapy really increase this risk mainly in the population with prediabetes. METHODS: A multicenter, cross-sectional, observational study was conducted to assess the relationship between statin therapy and glucose metabolism in 407 patients aged 63.1 years (11SD) diagnosed with dyslipidemia and prediabetes treated in specialized lipid clinics in Spain. RESULTS: Significant differences were found in HbA1c values among treatment groups (p=0.015). Patients treated with pitavastatin (1-4mg/day) showed the lowest HbA1c levels, with significant differences compared to patients treated with atorvastatin 40-80mg/day (p=0.016) and simvastatin 10-40mg/day (p=0.036). By contrast, patients treated with atorvastatin 40-80mg/day showed the highest HbA1c levels compared to those receiving atorvastatin 10-20mg/day (p=0.003), pitavastatin 1-4mg/day (p=0.016), pravastatin 20-40mg/day (p=0.027), rosuvastatin 5-10mg/day (p=0.043), and no statin treatment (p=0.004). Patients treated with simvastatin 10-40mg/day also had higher values than those treated with atorvastatin 10-20mg/day (p=0.016) and pitavastatin 1-4mg/day (p=0.036) or with no statin treatment (p=0.018). CONCLUSIONS: This study suggests that there are differences in the diabetogenic effect of statins. Simvastatin and high doses of atorvastatin may be associated with greater impairment in glucose metabolism than pitavastatin and other statins with less lipid-lowering potency such as pravastatin.

The underlying mechanisms for severe COVID-19 progression in people with diabetes mellitus: a critical review.

Diabetes mellitus (DM) has a high incidence of comorbidities among patients with severe coronavirus disease 2019 (COVID-19). The elevated prevalence of DM in the world population makes it a significant risk factor because diabetic individuals appear to be prone to clinical complications and have increased mortality rates. Here, we review the possible underlying mechanisms involved in DM that led to worse outcomes in COVID-19. The impacts of hyperglycemia side effects, secondary comorbidities, weakened innate and adaptive immunity, chronic inflammation, and poor nutritional status, commonly present in DM, are discussed. The role of the SARS-CoV-2 receptor and its polymorphic variations on higher binding affinity to facilitate viral uptake in people with DM were also considered. Clinical differences between individuals with type 1 DM and type 2 DM affected by COVID-19 and the potential diabetogenic effect of SARS-CoV-2 infection were addressed.

Two Cultivars of Ocimum basilicum Leaves Extracts Attenuate Streptozotocin-mediated Oxidative Stress in Diabetic Rats.

BACKGROUND AND OBJECTIVE: Leaves of basil plant (Ocimum basilicum) are often used for medicinal purposes because of their bioactive constituents, yet the antioxidant properties of this plant are not fully studied in the field of diabetes. The present study investigated the antioxidant property and anti-diabetic effect of two basil cultivars of Ocimum basilicum, 'Italian Genovese' and 'Thyrsiflora', in a Streptozotocin (STZ) rat model of diabetes . MATERIALS AND METHODS: Sixty adult Sprague Dawley rats (n = 10/group) were divided into 6 groups: Three non-diabetic and three diabetic groups that either did not receive any supplementation or were supplemented with the leaves extract of one or the other cultivar. After 13 weeks of feeding, all rats were sacrificed, pancreatic tissues were homogenized and used for evaluating oxidative DNA damage and dichlorofluorescein fluorescence (DCF) assay. Blood was collected for the measurements of glucose and insulin. RESULTS: The STZ caused oxidative stress in the diabetic group as evidenced by an increase in oxidative DNA damage and also caused DCF production in pancreatic tissues as compared to non-diabetic groups, (p<0.05). The STZ treatment resulted in hyperglycemia and low serum insulin level in diabetic rats. Supplementation with extracts of 'Italian Genovese' and 'Thyrsiflora' to the diabetic groups significantly abrogated the STZ-mediated effects (p<0.05). CONCLUSION: The results indicated that the extracts from the leaves of the two examined basil cultivars act as potent antioxidants and combat the STZ-mediated diabetogenic effect.

How do we know that statins are diabetogenic, and why? Is it an important issue in the clinical practice?

There is no doubt nowadays that statins exert a diabetogenic action. The evidence comes from observational studies, ran-domised trials, and meta-analyses. The relationship between statin use and new-onset type 2 diabetes is associated with statin potency and dose. It seems also to be stronger if the lowering effect is stronger and the low-density lipoprotein cholesterol level achieved is lower. The mechanisms underlying the development of diabetes in statin-treated patients are not completely understood. Generally, the increased insulin resistance and decreased insulin secretion are taken into account. However, it should be kept in mind that the cardiovascular risk reduction effect of statins outweighs the harm related to diabetes induc-tion. The patients at risk of diabetes development should be monitored with regard to the parameters of glucose metabolism. The introduction of preventive lifestyle modifications to prevent diabetes is recommended. New-onset diabetes should be managed according to the guidelines.