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Gut hormones appear to mediate impaired bone turnover markers in NAFLD with type 2 diabetes

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March 5, 2018

Adults with nonalcoholic fatty liver disease and type 2 diabetes had impaired collagen type 1 C-telopeptide suppression in response to an oral glucose tolerance test but not after an IV glucose infusion, study data show.

Tina Vilsbøll, MD, DMSc, professor and clinical manager at Steno Diabetes Center Copenhagen of the University of Copenhagen in Denmark, and colleagues evaluated data on eight adults with nonalcoholic fatty liver disease (NAFLD) and normal glucose tolerance (mean age, 55.5 years; 62.5% men; mean HbA1c, 33 mmol/mol), eight adults with NAFLD and type 2 diabetes (mean age, 65 years; 50% men; mean HbA1c, 50 mmol/mol), eight adults with type 2 diabetes alone (mean age, 58.5 years; 50% men; mean HbA1c, 43 mmol/mol) and nine healthy controls (mean age, 54 years; 55.6% men; mean HbA1c, 36 mmol/mol) to determine the influence of the gut on glucose-induced changes in plasma bone turnover markers.

At a screening visit and on two separate experimental days, participants underwent a 50-g 4-hour OGTT and a 4-hour isoglycemic IV glucose infusion (IIGI).

Compared with controls, participants with NAFLD and type 2 diabetes had lower collagen type 1 C-telopeptide (CTX; P = .034). Controls had higher procollagen type 1 N-terminal propeptide (P1NP) and osteocalcin compared with participants with NAFLD and type 2 diabetes (P1NP, P = .0016; osteocalcin, P < .001) and type 2 diabetes alone (P1NP, P = .036; osteocalcin, P < .001). Participants with NAFLD and normal glucose tolerance had higher P1NP and osteocalcin compared with participants with NAFLD and type 2 diabetes (P1NP, P = .003; osteocalcin, P = .016). Fasting levels of parathyroid hormone and vitamin D did not differ among the four groups.

Postprandial suppression of CTX during OGTT was attenuated in participants with type 2 diabetes alone compared with controls, and in participants with NAFLD and type 2 diabetes compared with participants with NAFLD and normal glucose tolerance. CTX suppression was similar during both OGTT and IIGI in participants with NAFLD and type 2 diabetes but was more pronounced during OGTT compared with IIGI in controls (P = .004), participants with NAFLD and normal glucose tolerance (P = .016) and participants with type 2 diabetes alone (P = .04). A reduced or absent OGTT-induced CTX suppression was evident in participants with NAFLD and type 2 diabetes compared with controls (P = .021) and participants with NAFLD and normal glucose tolerance (P = .038).

P1NP suppression on IIGI was more pronounced compared with OGTT in participants with NAFLD and type 2 diabetes (P = .016); no differences were observed among the other three groups.

“To our knowledge, the impact of NAFLD on bone health in patients with [type 2 diabetes] has not previously been investigated, and our findings suggest that NAFLD is a comorbidity that could explain variation in studies regarding bone health in [type 2 diabetes],” the researchers wrote. “Furthermore, we show that suppression of bone resorption (measured as CTX) is more pronounced when glucose is administered orally vs. intravenously (isoglycemic conditions) in healthy individuals, which supports the role of gut hormones as mediators of postprandial suppression of bone resorption acting either directly or perhaps via gut-mediated increases in insulin secretion.” – by Amber Cox

Disclosures: Vilsbøll reports she received lecture fees and unrestricted grants from, participated in advisory boards of and/or consulted for Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme/Merck, Novo Nordisk and Sanofi. Please see the study for all other authors’ relevant financial disclosures.