Postabsorptive hyperglucagonemia in patients with type 2 diabetes mellitus analyzed with a novel enzyme‐linked immunosorbent assay

Matsuo, Toshihiro; Miyagawa, Jun‐ichiro; Kusunoki, Yoshiki; Miuchi, Masayuki; Ikawa, Takashi; Akagami, Takafumi; Tokuda, Masaru; Katsuno, Tomoyuki; Kushida, Akira; Inagaki, Tadashi; Namba, Mitsuyoshi

doi:10.1111/jdi.12400

Cited by 45 publications

(47 citation statements)

References 38 publications

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“…The analyzed clinical characteristics of the participants are presented in Table, indicating a group comprising young adults with relatively well‐controlled diabetes, but with exhausted endogenous insulin production. The plasma glucagon level was 28.1 ± 17.7 pg/mL, which was comparable with that obtained in a previous report of Japanese patients with type 2 diabetes. However, the values were widely spread (5.7–95.2 pg/mL), and did not correlate with plasma glucose levels (33–401 mg/dL; Figure a).…”

Section: Resultssupporting

confidence: 88%

Dysregulated plasma glucagon levels in Japanese young adult type 1 diabetes patients

Kawamori

Katakami

Takahara

et al. 2018

J of Diabetes Invest

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Currently, the clinical dynamics of glucagon need to be revised based on previous data obtained from conventional glucagon radioimmunoassays. In the present study, we evaluated plasma glucagon levels in type 1 diabetes patients using a newly-developed sandwich enzyme-linked immunosorbent assay, and its association with clinical parameters and markers of diabetes complications were statistically assessed. The plasma glucagon level in 77 Japanese type 1 diabetes patients was 28.1 ± 17.7 pg/mL, and comparable with that reported previously for type 2 diabetes patients. However, the values were widely spread and did not correlate with plasma glucose values. Additionally, the average glucagon levels in patients in a hypoglycemic state (glucose level <80 mg/dL) did not increase (21.7 ± 12.2 pg/mL). The average glucagon level of patients experiencing hypoglycemia unawareness was significantly lower. Plasma glucagon levels evaluated using the new enzyme-linked immunosorbent assay were dysregulated in type 1 diabetes patients in respect to plasma glucose levels, suggesting dysregulation of secretion.

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Section: Resultssupporting

confidence: 88%

Dysregulated plasma glucagon levels in Japanese young adult type 1 diabetes patients

Kawamori

Katakami

Takahara

et al. 2018

J of Diabetes Invest

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“…In this study, as in the previous report [5][6][7][8][9], it was found that the average of fasting glucagon and FPG became higher with worsening of glucose tolerance, but there was no significant difference in fasting insulin and CPR level among NGT, preDM and DM group. Significant correlation was found between fasting glucagon level and the indicators of insulin sensitivity such as HOMA-IR and Matsuda index.…”

Section: Elevated Fasting Glucagon In Subjects With Impaired Glucose supporting

confidence: 82%

“…It is reported that fasting glucagon level is higher in T2DM compared to subjects with normal glucose tolerance (NGT) [3,4]. Inappropriate glucagon increase in the early phase of oral glucose tolerance test, and delayed glucagon suppression has been observed in diabetes patients [5][6][7][8][9], compared to immediate suppression of glucagon after glucose ingestion in the subjects with normal glucose tolerance. In normal physiology, a variety of factors have been known to influence glucagon regulation, such as insulin [10][11][12], GLP-1 [13][14][15][16][17][18][19], amino acids [20][21][22][23][24], autonomic nervous system [25][26][27], free fatty acids [28], and Zn 2+ ion [29].…”

mentioning

confidence: 99%

Basal glucagon hypersecretion and response to oral glucose load in prediabetes and mild type 2 diabetes

et al. 2019

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Dysregulation of glucagon secretion plays an important role in the pathogenesis of type 2 diabetes (T2DM). However it hasn't been elucidated involvement of glucagon dysregulation in pathophysiology of T2DM. Recently a new glucagon sandwich enzyme-linked immunosorbent assay (ELISA) became available that can measure plasma glucagon level with higher accuracy and simpler procedure than the conventional RIA method. We performed OGTT for adult subjects aged 20-69 years to define normal glucose tolerance (NGT, n = 25), borderline glucose intolerance (defined as pre-diabetes mellitus: preDM, n = 15), or diabetes mellitus (DM, n = 13), and we measured glucagon levels with this new ELISA method at fasting and during OGTT. Plasma glucose, insulin, glucagon and active GLP-1 were also measured. This study took place in diabetes outpatient clinic in Kitasato University Hospital and an affiliated outpatient clinic. PreDM and DM exhibited higher fasting plasma glucagon levels than NGT (34.4 ± 4.6 and 44.1 ± 5.0 vs. 20.6 ± 3.6 pg/mL), and statistical significance was observed between NGT and DM (p < 0.05). There was significant correlation between fasting glucagon level and indexes of insulin sensitivity. During OGTT, glucagon levels were less suppressed in DM and preDM than in NGT, whereas no apparent relationship was observed between glucagon and GLP-1 secretion. Significant positive correlation was observed between glucagon levels during OGTT and fasting TG. In conclusion, subjects with mild T2DM exhibited fasting hyperglucagonemia and insufficient suppression to oral glucose load compared to NGT subjects.

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“…In contrast to the complete lack of endogenous insulin, as assessed on the basis of a plasma C-peptide level below the detection limit, pancreatic glucagon was detectable, albeit at very low levels, in four out of seven patients with a total pancreatectomy. Cross-reactivity of glucagon-related peptides, such as oxyntomodulin and glicentin, in the glucagon assay has long been under debate, but sandwich enzyme-linked immunosorbent assays using a combination of C-and N-terminal antiglucagon antibodies, as used in the present study, have been reported to detect pancreatic glucagon with very small crossreactivity with other glucagon-related peptides 14,15 . Previous studies have suggested that pancreatic glucagon is synthesized and secreted from the gut [16][17][18] at levels detectable even in patients with total pancreatectomy 18 , and that such gut-derived glucagon is secreted in response to glucose intake and significantly affects glucose homeostasis 18 .…”

Section: Discussionmentioning

confidence: 90%

Insulin deficiency with and without glucagon: A comparative study between total pancreatectomy and type 1 diabetes

Niwano

Hiromine

Noso

et al. 2018

J of Diabetes Invest

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Aims/IntroductionPatients with a total pancreatectomy and type 1 diabetes are similar in regard to absolute insulin deficiency, but different in regard to glucagon, providing a unique opportunity to study the contribution of glucagon to glucose metabolism in an insulin‐dependent state. The aim of the present study was to investigate the contribution of glucagon to glucose homeostasis in complete insulin deficiency in vivo.MethodsA total of 38 individuals with a complete lack of endogenous insulin (fasting C‐peptide <0.0066 nmol/L) and whose glycemic control was optimized with an insulin pump during hospitalization were retrospectively studied. The basal insulin requirement, time‐to‐time adjustment of the basal insulin infusion rate, prandial insulin requirement and fasting plasma glucagon were compared between patients with a total pancreatectomy (n = 10) and those with type 1 diabetes (n = 28) after achievement of optimal glycemic control.ResultsTotal daily insulin (P = 0.03) and basal insulin (P = 0.000006), but not prandial insulin requirements, were significantly lower in total pancreatectomy patients than in type 1 diabetes patients. The basal percentage (basal insulin/total daily insulin) was also significantly lower in total pancreatectomy patients than in type 1 diabetes patients (15.8 ± 7.8 vs 32.9 ± 10.1%, P = 0.00003). An increase in the insulin infusion rate early in the morning was not necessary in most patients with a pancreatectomy. The fasting plasma glucagon concentration was significantly lower in total pancreatectomy patients than in type 1 diabetes patients (P = 0.00007), and was positively correlated with the basal insulin requirement (P = 0.038).ConclusionsThe difference in insulin requirements between total pancreatectomy and type 1 diabetes patients suggests a contribution of glucagon to the basal insulin requirement and dawn phenomenon.

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Postabsorptive hyperglucagonemia in patients with type 2 diabetes mellitus analyzed with a novel enzyme‐linked immunosorbent assay

Cited by 45 publications

References 38 publications

Dysregulated plasma glucagon levels in Japanese young adult type 1 diabetes patients

Dysregulated plasma glucagon levels in Japanese young adult type 1 diabetes patients

Basal glucagon hypersecretion and response to oral glucose load in prediabetes and mild type 2 diabetes

Insulin deficiency with and without glucagon: A comparative study between total pancreatectomy and type 1 diabetes

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