The joint effect of congenital hypothyroidism and hypercaloric diet consumption as triggers of type 2 diabetes mellitus

Introduction: Congenital hypothyroidism affects metabolic and thyroid programming, having a deleterious effect on bodyweight regulation promoting metabolic diseases. This work aimed to demonstrate the development of type 2 diabetes mellitus (T2D) in animals with congenital hypothyroidism, only by the consumption of a mild hypercaloric diet in the extrauterine stage. Methods: Two groups of female Wistar rats (n = 9): euthyroid and hypothyroid were used. Hypothyroidism was induced by a thyroidectomy with parathyroid reimplantation. Male offsprings post-weaning were divided into four groups (n = 10): euthyroid, hypothyroid, euthyroid + hypercaloric diet, and hypothyroid + hypercaloric diet. The hypercaloric diet consisted of ground commercial feed plus 20% lard and was administered until postnatal week 40. Bodyweight and energy intake were monitored weekly. Also, metabolic and hormonal markers related to cardiovascular risk, insulin resistance, and glucose tolerance were analyzed at week 40. Then, animals were sacrificed to perform the morphometric analysis of the pancreas and adipose tissue. Results: T2D was developed in animals fed a hypercaloric diet denoted by the presence of central obesity, hyperphagia, hyperglycemia, dyslipidemia, glucose tolerance, insulin resistance and hypertension, as well as changes in the cytoarchitecture of the pancreas and adipose tissue related to T2D. The results show that congenital hypothyroid animals had an increase in metabolic markers and an elevated cardiovascular risk. Conclusions: Congenital hypothyroid animals develop T2D, having the highest metabolic disturbances and a worsened clinical prognosis than euthyroid animals.