Calcium homeostasis is disturbed emanating from altered calciotropic hormone concentrations in type 2 diabetes mellitus (T2DM), a condition preceded by pre-diabetes. Disrupted calcium homeostasis has shown to promote insulin resistance and hyperglycaemia. However, the changes to calciotropic hormones in the pre-diabetic state is not known. Hence, this study investigated the effects of diet- induced pre-diabetes on calciotropic hormones in a pre-diabetic rat model. This study also sought to determine the association of calciotropic hormones with glycated haemoglobin (HbA1c) and insulin resistance during pre-diabetes. Twelve male Sprague Dawley rats were randomly assigned into two groups (n=6, per group): pre-diabetic (PD) and non-pre-diabetic (NPD). Fasting blood glucose (FBG), insulin, HbA1c and the homeostatic model assessment for insulin resistance (HOMA-IR) in addition to urine calcium, plasma calcium, parathyroid hormone (PTH), calcitonin, vitamin D and calcitriol concentrations were analysed at week 20. Correlation analysis was performed to examine the associations of calciotropic hormones with HOMA-IR and HbA1c. The results demonstrated increased concentrations of HbA1c, FBG, insulin and HOMA-IR in the PD group by comparison to NPD. Furthermore, plasma PTH, calcitonin, urine calcium, calcitriol and vitamin D levels increased along with unchanged plasma calcium concentrations in the PD group by comparison to NPD. Plasma PTH and calcitonin levels were positively correlated with HbA1c but not with HOMA-IR in the PD group. Plasma calcitriol levels were negatively correlated with HbA1c in the PD group. These observations suggest that calcium homeostasis is disturbed in diet- induced pre-diabetes but the body compensates for the changes by inducing an increase in calciotropic hormone levels. Furthermore, pre-diabetes may promote the development of hyperglycemia in T2DM through altering calciotropic hormone levels.

Derangements to the functioning of calcium-regulating organs have been associated with type 2 diabetes mellitus (T2DM), a condition preceded by pre-diabetes. Type 2 diabetes has shown to promote renal calcium wastage, intestinal calcium malabsorption and increased bone resorption. However, the changes to the functioning of calcium-regulating organs in pre-diabetes are not known. Subsequently, the effects of diet-induced pre-diabetes on the functioning of calcium-regulating organs in a rat model for pre-diabetes was investigated in this study. Male Sprague Dawley rats were separated into two groups (n=6, each group): non-pre-diabetic (NPD) group and a diet-induced pre-diabetic (DIPD) group for 20 weeks. After the experimental period, postprandial glucose and HOMA-IR were analysed in addition to plasma and urinary calcium concentrations. Gene expressions of intestinal vitamin D (VDR), intestinal calbindin-D9k, renal 1-alpha hydroxylase and renal transient receptor potential vanilloid 5 (TRPV5) expressions in addition to plasma osteocalcin and urinary deoxypyridinoline concentrations were analysed at week 20. The results demonstrated significantly increased concentrations of postprandial glucose, HOMA-IR and urinary calcium in addition to unchanged plasma calcium levels in the DIPD group by comparison to NPD. Renal TRPV5, renal 1-alpha hydroxylase, intestinal VDR and intestinal calbindin-D9k expressions were increased in the DIPD group by comparison to NPD. Furthermore, plasma osteocalcin levels were increased and urine deoxypyridinoline levels were decreased in the DIPD group by comparison to NPD. These observations may suggest that calcium-regulating organs compensate for the changes to calcium homeostasis by inducing increased renal calcium reabsorption, increased intestinal calcium absorption and decreased bone resorption followed by increased bone formation.