The Comparative Study on the Status of Bone Metabolism and Thyroid Function in Diabetic Patients with or without Ketosis or Ketoacidosis

Abstract

Purpose This study aims to identify changes in bone turnover markers and thyroid function in diabetic ketosis (DK) and diabetic ketoacidosis (DKA). Materials and Methods We compared data from the Department of Endocrinology at Shanghai Pudong Hospital from 2018 to 2020 on the pancreatic status and previous glucose control, bone transformation, calcium homeostasis, and thyroid function in groups with diabetes (DM alone, n=602), DK (n=232), and DKA (n=60). Similar comparisons were made in recurrent DK (A) (n=17) and single DK (A) (n=272). Results The fasting C-peptide level decreased significantly, but hemoglobin A1c (HbA1c) levels were higher in DK or DKA (p<0.05). Blood calcium and 25-hydroxyvitamin D3 (25-OH-VitD3) levels were significantly lower in DKA (p<0.05), but parathyroid hormone (PTH) levels remained constant across all three groups. The N-terminal middle molecular fragment of osteocalcin (N-MID) and β-C terminal cross-linking telopeptide of type 1 collagen (β-CTX) showed significant inverse alterations in DKA, regardless of gender or age (p<0.05). Otherwise, DKA significantly inhibited thyroid function (p<0.05). Furthermore, Spearman correlation analyses revealed a relationship between N-MID and HbA1c in DM alone (r=−0.27, p<0.01), while total triiodothyronine (TT3, r=0.62, p<0.01) or free T3 (FT3, r=0.61, p<0.01) in DK, and DKA (TT3, r=0.45, p<0.01; FT3, r=0.43, p<0.01). Multilinear regression analyses revealed that β-CTX (β=0.564), HbA1c (β=−0.196), TT3 (β=0.183), and 25-OH-VitD3 (β=−0.120) were the only independent determinants of N-MID in DM, whereas FT3 (β=0.491), β-CTX (β=0.315) in DK, and FT3 (β=0.420), β-CTX (β=0.367), TG (β=−0.278) in DKA. Only 25-OH-VitD3 was found to be significantly lower in recurrent DK (A) than in single onset DK (A) (p<0.05), and β-CTX (β=0.745) was found to be significantly independently associated with N-MID. Conclusion Our preliminary findings show a dramatic change in bone turnover markers in DM patients with DK and DKA, and this change may be related to thyroid function.

The Evolution of the Bone Turnover Marker in Patients Following Recovery from Diabetic Ketoacidosis

“…Parathyroid hormone (PTH), which stimulates calcium resorption, was evaluated in our previous study, and 25-OH-VitD3, a significant form reflecting the vitamin D reservoir and a precursor of active 1,25-OHVitD3, have been established as two critical hormones involved in blood calcium homeostasis. Despite previous research suggesting that DKA may inhibit the liver's production of 25-OH- VitD3, our findings indicate that DKA does not inhibit 25-OH-VitD3 synthesis, possibly due to the small sample size of DKA patients re-examined for bone turnover indicators [6]. Prior to this, a decrease in PTH was also observed, although it did not reach statistical significance.…”

“…Conversely, the bone resorption marker β-CTX showed an increase. It is highly conceivable that the change in NMID may be associated with thyroid dysfunction observed in DKA and the lower levels of 25-OHD3 in patients with recurrent DKA (RDK) compared to those with single DKA 6 . Importantly, our current study indicates that the change in NMID is not affected by the pH levels measured by blood gas tests or calcium levels.…”

“…Endocrinologists have recognized that patients with diabetes mellitus are at an increased risk of developing osteoporosis (OP), particularly in T1DM, and the mechanisms and clinical manifestations of OP caused by T1DM and T2DM are unique 5 . In our previous study and based on observations from daily clinical work, we discovered that OP is a frequent comorbidity in T2DM patients with diabetic ketosis (DK) or DKA identified as a risk factor for bone mass depletion or OP 6 . We observed a significant decrease in osteoblast activity, as indicated by the level of N-terminal middle molecular fragment of osteocalcin (NMID), and a noticeable increase in osteoclast activity, as indicated by the elevation of β-C-terminal cross-linking telopeptide of type 1 collagen (β-CTX).…”

Development and validation of a multivariable risk prediction model for identifying ketosis‐prone type 2 diabetes

“…Second, ketosis‐prone type 2 diabetes participants showed more severe bone destruction and more pronounced thyroid dysfunction. A similar conclusion was reached by Xu et al that ketosis or ketoacidosis may reduce the activity of osteoblasts, increase the activity of osteoclasts, and lead to β‐CTX increase, while damaging the hypothalamic–pituitary‐thyroid axis, resulting in low T3 syndrome 28 …”

The Relationship between Serum Iron and Thyroid Function in the Patients with Type 2 Diabetes

“…It is a multi-organ disease that impairs various organs. Alterations in markers related to bone metabolism and thyroid functions in DKA [ 6 ] have been reported previously, along with the thyroid of patients with Type 1 diabetes mellitus (T1DM) in whom the glycemic is generally stable [ 7 ]. About 15-30% of individuals with T1DM are complicated by Graves’ disease and Hashimoto's thyroiditis.…”