Accepted Article
Received Date : 24-Mar-2016 Revised Date
: 08-Nov-2016
Accepted Date : 23-Nov-2016 Article type
: Short Report
Short report
Undercarboxylated osteocalcin can predict insulin secretion ability in type 2 diabetes
Yuichi Takashi, Minae Koga, Yoko Matsuzawa, Jun Saito, Masao Omura, Tetsuo Nishikawa
Endocrinology and Diabetes Center, Yokohama Rosai Hospital
3211 Kozukue-cho, Kohoku-ku, Yokohama City, Kanagawa 222-0036, Japan
Corresponding author: Tetsuo Nishikawa 3211 Kozukue-cho, Kohoku-ku, Yokohama City, Kanagawa 222-0036, Japan E-mail:
[email protected] Telephone: +81-45-474-8111 Facsimile: +81-45-474-8323
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jdi.12601 This article is protected by copyright. All rights reserved.
Accepted Article
Short running title: The role of ucOC in type 2 diabetes
Abstract
There has been reported to be intimate relationship between diabetes and bone
metabolism including undercarboxylated osteocalcin (ucOC). On the other hand, data on the relationship between ucOC and glucose metabolism are limited in type 2 diabetes. We recruited 50 Japanese patients with type 2 diabetes and examined the association with ucOC on the insulin secretion, evaluated by both glucagon loading test (GLT) and meal tolerance test, and the prognosis of diabetes. UcOC was shown to correlate positively with ⊿C-peptide response (CPR) in GLT and CPR after meal taking (p=0.025, p=0.047). ucOC reflects the reserve capacity of β-cell function, such as the bolus insulin secretion ability in patients with type 2 diabetes.
Keywords: Insulin secretion, Type 2 diabetes, Undercarboxylated osteocalcin
Introduction
Undercarboxylated osteocalcin (ucOC) is a secreted protein produced by bone,
especially by osteoblast and enter the general circulation unlike osteocalcin which remains in bone1. UcOC can regulate insulin secretion and insulin sensitivity in rodents2,
3
. In humans, it is reported that ucOC is associated with insulin secretion, insulin
resistance and risk of type 2 diabetes in general population4-9, although the relationship
This article is protected by copyright. All rights reserved.
Accepted Article
between ucOC and glucose metabolism is still obscure. Furthermore, there were only a few previous reports suggesting the effect of ucOC on insulin secretion ability or future glycemic control especially in patients with type 2 diabetes. Therefore, we attempted to examine the association of ucOC with the insulin secretion, estimated by both glucagon loading test (GLT) and meal tolerance test (MTT) and their prognosis in patients with type 2 diabetes.
Subjects and Methods
Fifty Japanese patients with type 2 diabetes under written informed consent
were recruited. 41 men and 9 postmenopausal women were contained. They all were admitted our hospital in order to educate diabetes. The mean age, duration of diabetes, BMI, and HbA1c of the subjects were 59.2±1.43 y.o., 7.8±0.7 years, 26.2±0.5 kg/m2 and 9.4±0.2% (79±2 mmol/mol), respectively (Table 1). Participants who were treated with insulin and anti-osteoporosis drugs, such as vitamin D, vitamin K, bisphosphonate etc., were not included. Because vitamin K insufficiency increases ucOC level, participants who had anemia, hemorrhagic diathesis and hepatic disorder were also not included. 17, 19, 15, 19, 4 and 12 patients were treated with DPP-4 inhibitor, sulfonylurea, glinide, metformin, thiazolidinedione and alpha-glucosidase inhibitor, respectively. The prognosis of diabetes after 6 months was revealed in 41 patients. We could not follow up 9 patients’ data because they had moved to private clinician after leaving our hospital. They were allocated in two groups with lower and higher ucOC levels separated by the median ucOC level (2.16 ng/ml). Lower and higher ucOC groups contained 18 male and 3 female patients, and 15 male and 5 female patients.
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Accepted Article
Study methods We performed GLT and MTT on the third and second morning of
hospitalization. 1 mg of glucagon (Glucagon G Novo 1 mg®) was given intravenously and sequence of serum C-peptide response (CPR) levels were measured at 0 min and 6 min10 and 25 kcal/ideal body weight solid breakfast (60% carbohydrate, 25% fat, 15% protein) was given and serum CPR levels were measured at 0 min and 120 min. UcOC was determined in the third morning of hospitalization by electrochemiluminescence immunoassay (ECLIA) (EIDIA, Tokyo, Japan)11. The relationship between ucOC and
change in CPR in GLT and MTT were analyzed. We also analyzed the ratio of patients who were achieved less than HbA1c 7.0% after 6 months leaving our hospital in both lower and higher ucOC groups.
Statistical analysis Obtained data set are presented as means ± SEM. Correlations between ucOC
and each CPR were tested by using the Spearman’s correlation coefficient. Multiple regression analysis was employed. Fisher exact test was also employed to compare the difference of prognosis between lower and higher ucOC groups. Sex was changed into categorical variable and p
