Higher glucagon-to-insulin ratio is associated with elevated glycated hemoglobin levels in type 2 diabetes patients
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background/Aims: The importance of α-cell dysfunction in the pathogenesis of type 2 diabetes has re-emerged recently. However, data on whether relative glucagon excess is present in clinical settings are scarce. We aimed to investigate associations between glucagon-to-insulin ratio and various metabolic parameters. Methods: A total of 451 patients with type 2 diabetes naïve to insulin treatment were recruited. Using glucagon-to-insulin ratio, we divided subjects into quartiles according to both fasting and postprandial glucagon-to-insulin ratios. Results: The mean age of the subjects was 58 years, with a mean body mass index of 25 kg/m2. The patients in the highest quartile of glucagon-to-insulin ratio had higher glycated hemoglobin (HbA1c) levels. HbA1c levels were positively correlated with both fasting and postprandial glucagon-to-insulin ratios. Subjects in the highest quartile of postprandial glucagon-to-insulin ratio were more likely to exhibit uncontrolled hyperglycemia, even after adjusting for confounding factors (odds ratio, 2.730; 95% confidence interval, 1.236 to 6.028; p for trend < 0.01). Conclusions: Hyperglucagonemia relative to insulin could contribute to uncontrolled hyperglycemia in type 2 diabetes patients.
Abstract
Background/Aims: The importance of α-cell dysfunction in the pathogenesis of type 2 diabetes has re-emerged recently. However, data on whether relative glucagon excess is present in clinical settings are scarce. We aimed to investigate associations between glucagon-to-insulin ratio and various metabolic parameters. Methods: A total of 451 patients with type 2 diabetes naïve to insulin treatment were recruited. Using glucagon-to-insulin ratio, we divided subjects into quartiles according to both fasting and postprandial glucagon-to-insulin ratios. Results: The mean age of the subjects was 58 years, with a mean body mass index of 25 kg/m2. The patients in the highest quartile of glucagon-to-insulin ratio had higher glycated hemoglobin (HbA1c) levels. HbA1c levels were positively correlated with both fasting and postprandial glucagon-to-insulin ratios. Subjects in the highest quartile of postprandial glucagon-to-insulin ratio were more likely to exhibit uncontrolled hyperglycemia, even after adjusting for confounding factors (odds ratio, 2.730; 95% confidence interval, 1.236 to 6.028; p for trend < 0.01). Conclusions: Hyperglucagonemia relative to insulin could contribute to uncontrolled hyperglycemia in type 2 diabetes patients.
참고문헌 (40)
- Defronzo RA, "From the triumvirate to the ominous octet : a new paradigm for the treatment of type 2 diabetes mellitus", Diabetes, 58, pp.773~795 (2009)
- Fonseca VA, "Defining and characterizing the progression of type 2 diabetes", Diabetes Care, (32 Suppl 2), pp.S151~S156 (2009)
- Edgerton DS, "Glucagon as a critical factor in the pathology of diabetes", Diabetes, 60, pp.377~380 (2011)
- Li XC, "Current insights and new perspectives on the roles of hyperglucagonemia in non-insulin-dependent type 2 diabetes", Curr Hypertens Rep, 15, pp.522~530 (2013)
- Quesada I, "Physiology of the pancreatic alpha-cell and glucagon secretion : role in glucose homeostasis and diabetes", J Endocrinol, 199, pp.5~19 (2008)
- Liljenquist JE, "Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man", J Clin Invest, 59, pp.369~374 (1977)
- Ramnanan CJ, "Physiologic action of glucagon on liver glucose metabolism", Diabetes Obes Metab, 1(13 Suppl 1), pp.118~125 (2011)
- Tappy L, "Regulation of hepatic glucose production in healthy subjects and patients with non-insulin-dependent diabetes mellitus", Diabete Metab, 21, pp.233~240 (1995)
- Franklin I, "Beta-cell secretory products activate alpha-cell ATP-dependent potassium channels to inhibit glucagon release", Diabetes, 54, pp.1808~1815 (2005)
- Leung YM, "Insulin regulates islet alpha-cell function by reducing KATP channel sensitivity to adenosine 5’-triphosphate inhibition", Endocrinology, 147, pp.2155~2162 (2006)
- Ahren B, "Impaired glucose tolerance(IGT)is associated with reduced insulin-induced suppression of glucagon concentrations", Diabetologia, 44, pp.1998~2003 (2001)
- Shah P, "Impact of lack of suppression of glucagon on glucose tolerance in humans", Am J Physiol, 277, pp.E283~E290 (1999)
- Shah P, "Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus", J Clin Endocrinol Metab, 85, pp.4053~4059 (2000)
- Ipp E, "Impaired glucose tolerance: the irrepressible alpha-cell?", Diabetes Care, 23, pp.569~570 (2000)
- Larsson H, "Islet dysfunction in insulin resistance involves impaired insulin secretion and increased glucagon secretion in postmenopausal women with impaired glucose tolerance", Diabetes Care, 23, pp.650~657 (2000)
- Ahren B, "Beta-and alpha-cell dysfunction in subjects developing impaired glucose tolerance : outcome of a 12-year prospective study in postmenopausal Caucasian women", Diabetes, 58, pp.726~731 (2009)
- Unger RH, "Role of glucagon in the pathogenesis of diabetes : the status of the controversy", Metabolism, 27, pp.1691~1709 (1978)
- Charron MJ, "Lack of glucagon receptor signaling and its implications beyond glucose homeostasis", J Endocrinol, 224, pp.R123~R130 (2015)
- Cho YM, "Targeting the glucagon receptor family for diabetes and obesity therapy", Pharmacol Ther, 135, pp.247~278 (2012)
- Dunning BE, "Alpha cell function in health and disease : influence of glucagon-like peptide-1", Diabetologia, 48, pp.1700~1713 (2005)
- Rohrer S, "Impaired crosstalk between pulsatile insulin and glucagon secretion in prediabetic individuals", J Clin Endocrinol Metab, 97, pp.E791~E795 (2012)
- Jin SM, "Glucagon", insulin ratio in preoperative screening before pancreatic surgery : correlation with hemoglobin A1C in subjects with and without pancreatic cancer, 2014, pp.47, 493~499
- 문준성, "Pancreatic α-Cell Dysfunction in Type 2 Diabetes: Old Kids on the Block", Diabetes and Metabolism Journal, 39(1), pp.1~9 (2015), 대한당뇨병학회
- Rivera N, "A novel glucagon receptor antagonist, NNC 25-0926, blunts hepatic glucose production in the conscious dog", J Pharmacol Exp Ther, 321, pp.743~752 (2007)
- Friedewald WT, "Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge", Clin Chem, 18, pp.499~502 (1972)
- Abdul-Ghani M, "Fasting hyperglycemia impairs glucose-but not insulin-mediated suppression of glucagon secretion", J Clin Endocrinol Metab, 92, pp.1778~1784 (2007)
- Ahlkvist L, "Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice", J Endocrinol, 228, pp.171~178 (2016)
- Baron AD, "Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics", Diabetes, 36, pp.274~283 (1987)
- Consoli A, "Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM", Diabetes, 38, pp.550~557 (1989)
- Yoon KH, "Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea", J Clin Endocrinol Metab, 88, pp.2300~2308 (2003)
- Reaven GM, "Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus", J Clin Endocrinol Metab, 64, pp.106~110 (1987)
- Umpaichitra V, "C-peptide and glucagon profiles in minority children with type 2 diabetes mellitus", J Clin Endocrinol Metab, 86, pp.1605~1609 (2001)
- Ferrannini E, "Association of fasting glucagon and proinsulin concentrations with insulin resistance", Diabetologia, 50, pp.2342~2347 (2007)
- Liu Z, "Insulin and glucagon regulate pancreatic α-cell proliferation", PLoS One, 6, pp.e16096~ (2011)
- Ohn JH, "10-Year trajectory of β-cell function and insulin sensitivity in the development of type 2 diabetes : a community-based prospective cohort study", Lancet Diabetes Endocrinol, 4, pp.27~34 (2016)
- Mohan V, "Clinical profile of lean NIDDM in South India", Diabetes Res Clin Pract, 38, pp.101~108 (1997)
- Chang SA, "Body mass index is the most important determining factor for the degree of insulin resistance in non-obese type 2 diabetic patients in Korea", Metabolism, 53, pp.142~146 (2004)
- Kim DJ, "Insulin secretory dysfunction and insulin resistance in the pathogenesis of Korean type 2 diabetes mellitus", Metabolism, 50, pp.590~593 (2001)
- Bessho M, "Glycaemic instability correlates with a hyperglucagonaemic response in patients with type 1 diabetes without residual beta-cell function", Diabetes Res Clin Pract, 102, pp.e38~e40 (2013)
- Dinneen S, "Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM", Diabetologia, 38, pp.337~343 (1995)