The role of enteric hormone GLP-2 in the response of bone markers to a mixed meal in postmenopausal women with type 2 diabetes mellitus

Abstract

BackgroundType 2 diabetes mellitus (T2D) is a complex disease associated with several chronic complications, including bone fragility and high fracture risk due to mechanisms not yet fully understood. The influence of the gastrointestinal tract and its hormones on bone remodeling has been demonstrated in healthy individuals. Glucagon-like peptide 2 (GLP-2), an enteric hormone secreted in response to nutrient intake, has been implicated as a mediator of nutrient effects on bone remodeling. This study aimed to analyze the dynamics of bone resorption marker C-terminal telopeptide of type I collagen (CTX), bone formation marker osteocalcin, and GLP-2 in response to a mixed meal in diabetic postmenopausal women.MethodsForty-three postmenopausal women with osteopenia or osteoporosis (20 controls – group CO – and 23 diabetic – group T2D) were subjected to a standard mixed meal tolerance test, with determination of serum CTX, plasma osteocalcin and serum GLP-2 concentrations at baseline and 30, 60, 120 and 180 minutes after the meal.ResultsT2D women had higher body mass index as well as higher femoral neck and total hip bone mineral density. At baseline, luteinizing hormone, follicle-stimulating hormone, osteocalcin and CTX levels were lower in group T2D. In response to the mixed meal, CTX and osteocalcin levels decreased and GLP-2 levels increased in both groups. The expected CTX suppression in response to the mixed meal was lower in group T2D.ConclusionsBone turnover markers were significantly reduced in T2D women at baseline. Confirming the role of nutrient intake as a stimulating factor, GLP-2 increased in response to the mixed meal in both groups. Importantly, CTX variation in response to the mixed meal was reduced in T2D women, suggesting abnormal response of bone remodeling to nutrient intake in T2D.

Glucocorticoid-Induced Insulin Resistance in Men Is Associated With Suppressed Undercarboxylated Osteocalcin

“…The suppression of bone remodeling markers, including tOC, ucOC, P1NP, and β‐CTx, has previously been reported following nutrient intake such as an oral glucose tolerance test or a mixed meal or glucose infusion during an euglycemic‐hyperinsulinemic clamp . In support of previous findings, we report that tOC, ucOC, P1NP, and β‐CTx are suppressed in healthy men after insulin and glucose infusion, supporting the bidirectional feed‐forward loop between osteocalcin and glucose.…”

Glucagon‐like peptide‐2: A potential role in equine insulin dysregulation

“…The consistently high circulating GLP‐2 concentration in ponies with ID may be significant, as any loss of diurnal variability would presumably contribute to persistent pathological change and disease severity. However, the GLP‐2 concentrations in the ID cohort were lower than post‐prandial concentrations (>4 ng/mL) reported in patients with type‐2 diabetes mellitus (T2DM) , which may reflect the different underlying pathological processes of these two conditions. Given that an inverse relationship between GLP‐2 secretion and insulin sensitivity has been reported , further studies on the relationship between GLP‐2 secretion and equine ID are justified.…”

<p>Type 1 Diabetes and Bone Fragility: Links and Risks</p>

“…However, neither fluctuations in glucose during 24 hours28 nor clamps with hypoglycemia and hyperglycemia32 alter the levels of CTX or P1NP in patients with T1D. During a meal or an oral glucose tolerance test, levels of bone turnover markers decrease in healthy individuals and in patients with T2D 33,34. The influence of meals on bone turnover was similar between T1D, T2D and controls based on the diurnal study 28.…”