Identification et stratification du risque cardiométabolique lié à l'obésité ou au diabète de type 2 chez les femmes en surpoids ou obèse post-ménopausées : exploration d’indicateurs biologiques & morphologiques

Obesity increases the risk of cardiometabolic diseases such as type 2 diabetes, dyslipidemia and hypertension. The cardiometabolic risk factors include traditional risk factors as well as new emerging factors including insulin resistance, ectopic fat accumulation and inflammation caused by impaired secretion of adipose tissue adipokines. All these risk factors are regrouped under the term of global cardiometabolic risk. Some groups of patients demonstrated greater risk than others. Moreover, usual clinical and biological parameters may not be sufficient to identify such groups. In postmenopausal women, the loss of protection conferred by estrogen and changes in the distribution of body fat significantly increase the cardiometabolic risk. In addition, subjects with type 2 diabetes are considered at high cardiovascular risk especially when glycemic control targets are not met. The objective of this thesis is to assess the relevance and effectiveness of anthropometric, morphological, biological and composite indicators in the assessment and classification of cardiometabolic risk associated with obesity or type 2 diabetes. Using data collected among post-menopausal women and sedentary overweight or obese, our results showed that the Body adiposity index was a good indicator of total body fat and its variation however, there were differences between this index and total fat mass as determined by DXA when considering correlations with cardiometabolic risk factors. For the Visceral adiposity index, although this indicator was sensitive to changes in visceral fat changes after weight loss, it was not better than body mass index or waist circumference in predicting cardiometabolic risk. With regard to the high molecular weight adiponectin as a biological indicator, our analyses did not confirm its superiority over the determination of total adiponectin alone. Furthermore these two indicators are sensitive to acute hyperinsulinemia. A sub-group of obese people demonstrated high insulin sensitivity. The discrimination of this group versus those who are obese but insulinresistant is important for risk stratification. Our results showed that, the whole body insulin sensitivity outperform muscle or liver insulin sensitivity indices when classifying these two groups. In addition, women who demonstrated a hepatic insulin resistance were more at risk of dysglycemia and whole body insulin resistance than those with muscle insulin resistance. We also showed among subjects with type 2 diabetes and poor glycemic control, that the initiation of insulinotherapy improved glycemic control and reduced the accumulation of the epicardial fat thickness as measured by ultrasonography. Moreover, this ectopic fat showed a tendency to be more reduced with insulin Detemir than with insulin Glargine. In conclusion, the cardiometabolic iv risk stratification remains complex. The choice of an indicator in risk stratification should be done while taking into account its strengths and limitations. In addition to the indicators explored in this thesis, there are still no established threshold values. Therefore, it is not always possible to compare the risk stratification between different studies. Future investigations are needed to meet this goal and allow a more standardized use of these indicators.

Keyphrases: ménopause, Obesity, Menopause, Epicardial fat thickness, Type 2 diabetes, Total adiponectin