Type 2 diabetes is a metabolic disease with genetic and environmental factors interacting with multiple organ damage, and the skeletal system is no exception; insulin deficiency or resistance and hyperglycemia and glycosylation end products have adverse effects on bone metabolism; islet B-cell function is positively associated with 25(OH)VD levels. A cross-sectional study involving 5677 patients found that serum 25(OH)VD levels were lower in patients with newly diagnosed type 2 diabetes and impaired glucose tolerance compared to age-, sex-, and race-matched control populations. Both plasma glucose and total insulin levels under the standard 75g glucose tolerance test curve were negatively correlated with serum 25(OH)VD levels.
It was found that HbA1C was negatively correlated with serum 25(OH)VD levels in type 2 diabetic patients, and was not correlated with lumbar spine BMD, but was negatively correlated with femoral neck BMD. It may be due to poor glycemic control and impaired renal microcirculation, resulting in reduced 1a-hydroxylase activity and decreased 1,25(OH)2VD3 production. And the reduced level of 1,25(OH)2VD3 may not only impair the function of pancreatic B-cells and increase blood glucose; but also reduce intestinal calcium absorption, decrease bone calcium deposition and osteoblast activity, which leads to bone loss. The femoral neck has a relatively poor blood supply compared to the lumbar spine, and the microangiopathy of diabetes aggravates this condition, resulting in the femoral neck being more prone to bone loss than the lumbar spine. In addition, the lumbar spine is more prone to age-related osteomalacia than the femoral neck, resulting in high measured bone mineral density results, which may also contribute to the lack of low bone mineral density in the lumbar spine.
Although patients with type 2 diabetes have a positive effect on BMD because of obesity, hyperinsulinemia, and leptin resistance; this may be due to increased peripheral aromatase activity in obese individuals, which increases the conversion of testosterone to estradiol; both high body weight and hyperinsulinemia have a stimulating effect on bone formation; leptin inhibits osteoblast differentiation and suppresses osteoclastogenesis; all three are beneficial in maintaining bone mass in patients with type 2 diabetes . However, as the disease progresses, pancreatic B-cell function gradually fails, insulin secretion decreases, HbA1C increases, metabolic disorders and vascular lesions worsen, leading to increased urinary calcium excretion and decreased 1,25(OH)2VD3 synthesis, which results in decreased osteoblast activity and increased osteoclast activity, followed by decreased bone mass.