Page 166 - fbkCardioDiabetes_2017

142 Thyroid Dysfunction, Diabetes and the Cardiac Link

insulin stimulated glucose uptake, increase hepatic itive patients. Positive TPO antibodies have been re-
glucose output and impaired lipid homeostasis. ported as high as 38% of diabetic individuals and are
a strong predictor for the development of future hy-
Prevalance of thyroid disease and diabetes pothyroidism. The association between autoimmune
thyroid disease and type 1 diabetes has been rec-
The earliest study on the prevalence of thyroid dys-
function wasfrom the Wickhamsurvey, which showed ognized as a variant of autoimmune poly glandular
a prevalence of thyroid dysfunction in male adults syndrome referred to as APS3 variant. Common sus-
in England to be 6.6%. The mean annual incidence ceptibility genes have been acknowledged to confer
of spontaneous hypothyroidism during a 20-year fol- a risk for development of both autoimmune thyroid
low-up period was 3.5 per 1000 and 0.6 per 1000 in disease and type 1 diabetes mellitus.
surviving females and males, respectively. A raised
TSH or positive antibodies alone or in combination Peripheral Effects of Thyroid Hormones on
were associated with an increased risk of future hy- Insulin Secretion and Sensitivity
pothyroidism[2]. The annual risk of developing hy- Thyroid hormone actions on peripheral tissues fur-
pothyroidism was 4 percent when they had a higher ther explain the global effects of thyroid function on
TSH than 2 and raised antibodies. The risk impart- insulin secretion, action and glucose uptake. Insulin
ed by TSH and antibodies were additive and inde- secretion is under direct control of thyroid axis. In
pendent of each factor.In the Colorado prevalence hypothyroidism, glucose-induced insulin secretion
study, 9.5 percent had an elevated thyroid-stimu- by the β-cells is reduced. Experimental hypothyroid-
lating hormone, while another 2.2% had a low TSH. ism in healthy subjects affect glucose uptake. The
Recent Indian data suggest that 3.9% of the study rates of glucose oxidation and glycogen synthesis
population was found to have overt hypothyroidism are decreased in hypothyroidism (Figure 1). Insulin
and a further 9.4% have subclinical thyroid disease. sensitivity further improves in parallel with increasing
The prevalence of thyroid dysfunction increases with thyroxine concentrations across the normal range.
advancing age and is higher in women at 11.4% com- Hypothyroidism is also associated with reduced re-
pared to 6.2% in men. nal clearance of insulin leading to reduced require-
The co-existence of diabetes mellitus and hypothy- ments of further insulin secretion[4]. Clinically, insu-
roidism is very common in day-to-day clinical prac- lin requirements are decreased in diabetic patients
tice. There is evolving data that patients with dia- in untreated hypothyroidism increasing the risk of
betes are more prone to thyroid dysfunction when hypoglycemia. Correction of hypothyroidism will im-
compared to the general population. Patients with prove insulin doses to basal requirements. Recurrent
organ-specific autoimmune disease are at a risk of hypoglycemia despite correction of hypothyroidism
developing other autoimmune disorders. Women would need exclusion of associated pituitary or ad-
with type 1 diabetes show a very high prevalence of renal failure.
hypothyroidism at 31% with an overall prevalence of Gene array studies of human skeletal muscle in hy-
thyroid disease with diabetes at 13.4 %[3]. The prev- pothyroid and euthyroid subjects suggest a marked
alence of thyroid dysfunction in type 2 diabetes from impact on glucose transporter expression with down
Greece and Saudi Arabia are 12.3 and 16 % respective- regulation of GLUT5 in hypothyroidism. In these stud-
ly. One recent report from India suggested that up to ies, GLUT4 expression was not significantly altered.
30 % of patients with type 2 diabetes had some form Animal models indicate impaired GLUT4 transloca-
of thyroid dysfunction. In this particular cohort, 16% tion to the plasma membrane and negative regula-
had sub-clinical hypothyroidism, 11% had overt hypo- tion of enzymatic breakdown of intracellular glucose
thyroidism, 2% sub-clinical hyperthyroidism and 1.5% in both hyperthyroidism and hypothyroidism. This
had frank hyperthyroidism.The prevalence of thyroid appears to depend critically on the intracellular gen-
disorder in the diabetic population is higher at 13.4 % eration of free T3 as polymorphisms of DIO2 with de-
and women tend to show an even higher prevalence creased T3 generation are associated with some de-
at 31.4% compared to male type 2 diabetic subjects. gree of insulin resistance.Insulin resistance has been

Thyroid autoimmunity remains the most frequent au- also reported in subclinical hypothyroidism, adding
toimmune disorder associated with type 1 diabetes. one more possible mechanism to the association of
This was shown in a cross-sectional study involving sub-clinical hypothyroidism and cardiovascular risk.
1419 children with type 1 diabetes mellitus, where 3.5% In subclinical hypothyroidism, there is diminished
had Hashimoto’s thyroiditis. A 3.5-fold increased risk rate of insulin stimulated glucose transport caused
of autoimmune thyroiditis was noticed in GADA pos- by altered expression of glucose transporter GLUT

GCDC 2017