Improved glycemic control due to sitagliptin is not related to cortisol or the surrogate marker IGFBP-1 for hepatic insulin sensitivity.
OBJECTIVE
Elevated cortisol levels and dysregulated insulin-like growth factor binding protein-1 (IGFBP-1; a marker of hepatic insulin sensitivity) are both related to insulin resistance and glucose abnormalities. It is unknown whether improvement in these parameters is related to improved glucose metabolism during treatment with sitagliptin.


OBJECTIVE
To determine whether improved insulin sensitivity and beta-cell function during treatment with sitagliptin is related to lower cortisol levels and/or improved regulation of IGFBP-1 in patients with recent acute coronary syndrome (ACS) and newly discovered glucose abnormalities.


METHODS
Samples were taken from The BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction (BEGAMI) trial, a double-blinded, placebo-controlled randomized clinical trial on the efficacy and safety of sitagliptin for patients with ACS and newly discovered glucose abnormalities.


METHODS
Cardiology departments (cardiac ICU and outpatient clinic) in two hospitals in Stockholm, Sweden.


METHODS
Subjects hospitalized (or recently hospitalized) for ACS, in whom an oral glucose tolerance test revealed previously unknown glucose abnormalities.


METHODS
Subjects were randomized to sitagliptin 100mg once daily (n=34) or placebo (n=37) for twelve weeks. Oral glucose tolerance test (OGTT) and randomization occurred after stabilization median 7 days after ACS.


METHODS
Fasting serum cortisol and IGFBP-1 were analyzed before OGTT, around 8a.m., and after at 10a.m. The latter time point was chosen as the spread in cortisol levels around is small then, allowing improved chances to detect differences between groups.


RESULTS
Glucose tolerance and insulin sensitivity improved in both groups, while HbA1c and indices of β-cell function improved only in the sitagliptin group as reported previously. Both groups displayed decreased cortisol levels around 10a.m. (from 338±21 to 278±14 nmol/L, p=0.038, in the sitagliptin group; from 343±17 to 302±15 nmol/L, p=0.017, in the placebo group), and improved correlation between fasting log-IGFBP-1 and insulin.


CONCLUSIONS
These findings suggest that a stress-related elevation in cortisol may have negative impact on glucose tolerance in patients with recent ACS. However, improved glycemic control with sitagliptin does not appear to be related to changes in cortisol levels or hepatic insulin sensitivity as assessed by IGFBP-1.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 17176 Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, 17176 Stockholm, Sweden. Electronic address: Lisa.Arnetz@karolinska.se.
Lisa
L
Arnetz
Cardiology Unit, Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden. Electronic address: camilla.hage@karolinska.se.
Camilla
C
Hage
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 17176 Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, 17176 Stockholm, Sweden. Electronic address: neda.ekberg@ki.se.
Neda Rajamand
NR
Ekberg
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 17176 Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, 17176 Stockholm, Sweden. Electronic address: michael.alvarsson@karolinska.se.
Michael
M
Alvarsson
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 17176 Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, 17176 Stockholm, Sweden. Electronic address: kerstin.brismar@ki.se.
Kerstin
K
Brismar
Cardiology Unit, Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden. Electronic address: anna.norhammar@karolinska.se.
Anna
A
Norhammar
Cardiology Unit, Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden. Electronic address: linda.mellbin@karolinska.se.
Linda
L
Mellbin
D054058:Acute Coronary Syndrome / Q000150:complications; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D013548:Sweden; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D006854:Hydrocortisone; D007004:Hypoglycemic Agents; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D000068900:Sitagliptin Phosphate; C583557:IGF1 protein, human; C032231:IGFBP1 protein, human; C517652:hemoglobin A1c protein, human
Beta-cell function; Cortisol; Diabetes; IGFBP-1; Insulin resistance; Sitagliptin