Diabetes mellitus is an incurable progressive disease, characterized by elevated blood glucose levels, which lead to the development of micro- and macrovascular complications. Although the etiopathology of the disease remains unclear, it seems to be multifactorial, with an important interaction between genetics and environmental causes. Currently, the genetics of type 2 diabetes (T2D) is poorly understood. The recent advance of the genetic technologies and with a better understanding of genetics, more than 120 distinct genetic loci, with more than 150 variants, have been identified that may be involved in the pathogenesis of T2D. However, as these variants can account for only approximately 20% of the heritability of T2D, there is an obvious need for additional approaches to identify susceptibility genes or genetic mechanisms involved in the development of this disease. There is a growing number of genes found to be related to T2D; however, their individual impact on the pathogenesis of the disease appears to be low, while silencing of protective genes may also contribute to the development of this disease. The present review attempts to summarize our current knowledge in the field of genetics of T2D, highlighting the possible practical applications for each approach.

With the pandemic of type 2 diabetes (T2D), there is an ever-increasing need to fully understand the underlying mechanisms of the disease. Type 2 diabetes shows a high heritability risk (25-80%); however, genes account only for 10% of this risk. From all the risk factors for diabetes, epigenetic mechanisms have the highest statistical scoring in explaining the disease. A multitude of organ-specific epigenomic changes have been linked to type 2 diabetes. Nutritional influences, mainly in the early life, physical activity level, environmental toxins act as epigenetic factors and the recognized epigenetic changes can represent a therapeutical target, new drugs being currently in development for this application. Our current review focuses on the most common epigenetic modifications linked to type 2 diabetes or insulin resistance, the potentially emerging epigenetic-related interventions and pharmacoepigenetic knowledge.

Aim: This study evaluated the correlations between metabolic parameters and reproductive health data in women with type 2 diabetes mellitus (T2DM).Material and methods: In this observational retrospective study, data from the medical records of 324 adult women with T2DM attending their regular diabetes check-ups were collected and analyzed (i.e., anthropometric parameters at first outpatient visit and yearly thereafter, first recorded HbA1c and all HbA1c for the entire follow-up duration, as well as obstetrical/gynecological information).Results: Age at the diagnosis of T2DM correlated positively with age at menarche (r = 0.21, [95% CI: 0.09, 0.31], p = 0.0002) and age at menopause (r = 0.18 [95% CI: 0.07, 0.29], p <0.01). Age at menarche correlated negatively with mean weight (r = –0.21 [95% CI: –0.31, –0.10], p: 0.0002) and mean BMI (–0.22 [–0.32, –0.11], p <0.0001) over the follow-up time. Patients with shorter time difference between age at menarche and age at onset of T2DM (≤45 years) had higher mean weight (83.8 ± 14.5 kg vs. 78.4 ± 16.0 kg, p = 0.0001), BMI (33.2 ± 5.6 kg/m2 vs. 31.8 ± 5.7 kg/m2, p <0.05), and HbA1c over time (6.9 ± 0.8% vs. 6.6 ± 0.9%, p <0.0001). Women with T2DM with earlier menarche (<12 years old), with irregular menses during their reproductive life, and ≥3 pregnancies had higher overall BMI, but mean HbA1c were not significantly different. However, women diagnosed with T2DM before menopause had a higher mean HbA1c over time (7.1 ± 0.8% vs. 6.7 ± 0.9%, p <0.01).Conclusion: The BMI correlated with several indicators of reproductive health (earlier menarche, irregular menses, and higher number of pregnancies), while earlier onset of T2DM influenced metabolic control in women with T2DM.