Mini‐review: Glucagon responses in type 1 diabetes – a matter of complexity

Bengtsen, Mads Bisgaard; Møller, Niels

doi:10.14814/phy2.15009

Cited by 28 publications

(25 citation statements)

References 53 publications

(88 reference statements)

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“…Previous studies have reported that patients with T1DM excessively secrete glucagon after a mixed-meal stimulation as opposed to individuals without diabetes [13]. In healthy individuals, blood glucagon levels reach a peak 30 -60 min after consuming a mixed-meal (700 kcal; 100 g of carbohydrate, 26 g of protein, and 22 g of fat), return to near baseline after 120 min, then increase again; however, the range of fluctuation is small compared to patients with diabetes [14].…”

Section: Discussionmentioning

confidence: 97%

“…In healthy individuals, blood glucagon levels reach a peak 30 -60 min after consuming a mixed-meal (700 kcal; 100 g of carbohydrate, 26 g of protein, and 22 g of fat), return to near baseline after 120 min, then increase again; however, the range of fluctuation is small compared to patients with diabetes [14]. The excessive secretion of glucagon after a mixed-meal stimulation in pa-tients with T1DM relates to low paracrine insulin secretion, which could cause postprandial hyperglycemia due to hyperglucagonemia in patients with T1DM [13].…”

Section: Discussionmentioning

confidence: 99%

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The Difference in Glucagon Response to Breakfast Between Non-Obese Patients With Long-Duration Type 1 and Type 2 Diabetes

Hamasaki¹

2022

J Endocrinol Metab

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Background: A balanced action of insulin and glucagon is essential for treating diabetes. This study aimed to assess the change in blood glucagon levels from fasting to a postprandial state and to compare them between patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM).Methods: This study enrolled patients with T1DM (n = 13) who had undetectable serum C-peptide levels (< 0.02 ng/mL) and patients with T2DM (n = 13) whose age, gender, and body mass index were matched to cases (1:1) as controls. Plasma glucose, serum C-peptide, and plasma glucagon in fasting and 2 h after consuming a standard breakfast for diabetic patients were measured and compared between groups.Results: There were no significant differences in plasma glucose and hemoglobin A1c levels between patients with T1DM and T2DM. However, fasting plasma glucagon levels were significantly lower in patients with T1DM than those in patients with T2DM (19.2 ± 13.0 pg/mL vs. 31.6 ± 18.3 pg/mL, P = 0.029). Furthermore, the glucagon's response to a standardized meal for diabetic patients differed between patients with T1DM and T2DM. Conclusions:The significant difference in glucagon response to the meal may be caused by the abnormal postprandial secretion of glucagon in patients with T1DM. The nutrient ratio of the meal may also influence glucagon secretion.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

The Difference in Glucagon Response to Breakfast Between Non-Obese Patients With Long-Duration Type 1 and Type 2 Diabetes

Hamasaki¹

2022

J Endocrinol Metab

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“…Finally, type 1 diabetes increases the risk of associated autoimmune disease, including adrenocortical failure, and people with concomitant Addison disease and type 1 diabetes have increased risk both of hypoglycemia and adrenal crisis [ 64 , 65 ]. It would appear advisable to incorporate the existence of additional organ dysfunction including HAAF in the setting of therapeutic targets, perhaps aiming at less-strict glycemic windows in closed-loop systems likely to dominate the future; adding adjustable glucagon infusion to such systems could be considered in selected patients with defective counterregulation [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Experimentally Induced Hypoglycemia-associated Autonomic Failure in Humans: Determinants, Designs, and Drawbacks

Bengtsen

Møller

2022

Journal of the Endocrine Society

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Introduction Iatrogenic hypoglycemia remains one of the leading hindrances of optimal glycemic management in insulin-treated diabetes. Recurring hypoglycemia leads to a condition of hypoglycemia-associated autonomic failure (HAAF). HAAF refers to a combination of (i) impaired hormonal counter regulatory responses and (ii) hypoglycemia unawareness to subsequent hypoglycemia, substantially increasing the risk of severe hypoglycemia. Several studies since the 1990ies have experimentally induced HAAF yielding variable results. The aim of this review is to assess the varying designs, clinical outcomes, potential assets and drawbacks related to these studies. Method A systemic literature search was conducted on PubMed and Embase in the winter 2021 to include all human studies which attempting to experimentally induce HAAF. In different combinations, the search terms used were “hypoglycemia-associated autonomic failure", “HAAF”, “hypoglycemia” “recurring”, “recurrent”, “repeated”, “consecutive”, and “unawareness” yielding 1,565 publications. Inclusion criteria were studies who had aimed at experimentally inducing HAAF and measuring outcomes of hormonal counter regulation and awareness of hypoglycemia. Results The literature search yielded 27 eligible publications of which 20 were successful in inducing HAAF with statistical significantly impairing both hormonal counter regulation and impairing awareness of hypoglycemia to subsequent hypoglycemia. Several factors were of significance as regards inducing HAAF; foremost, the duration of antecedent hypoglycemia should be at least 90 minutes and blood glucose should be maintained below 3.4 mmol/L. Other important factors to consider are the type of participants, insulin dosage, and the risk of unintended hypoglycemia prior to the study. Conclusion Here we have outlined the most important factors to take into consideration when designing a study aimed at inducing HAAF including to take into consideration other disease states susceptible to hypoglycemia thus hopefully clarifying the field and allowing qualified studies in the future.

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“…110,111 Individuals with T2DM, as opposed to nondiabetic subjects, display glucagon hypersecretion after meals, thereby potentially contributing to insulin resistance. 112 Thus, patients with diabetes have lost the first two lines of defense and are particularly vulnerable to changes in epinephrine release, [113][114][115] which further increases the risk of recurrent and severe hypoglycemia. 116 In addition to these well-described counter-regulatory hormonal responses, the central nervous system (CNS) also plays a critical role in the response to hypoglycemia (Figure 1).…”

Section: Physiologic Defenses Against Hypoglycemiamentioning

confidence: 99%

“…Furthermore, β‐cell destruction is also linked to the loss of α‐cell glucagon secretory response to hypoglycemia which prevents hypoglycemia‐triggered increases in glucagon levels 110,111 . Individuals with T2DM, as opposed to nondiabetic subjects, display glucagon hypersecretion after meals, thereby potentially contributing to insulin resistance 112 . Thus, patients with diabetes have lost the first two lines of defense and are particularly vulnerable to changes in epinephrine release, 113–115 which further increases the risk of recurrent and severe hypoglycemia 116 …”

Section: Introductionmentioning

confidence: 99%

Pathophysiology and management of hypoglycemia in diabetes

Sanchez‐Rangel

Deajon‐Jackson

Hwang

2022

Annals of the New York Academy of Sciences

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In the century since the discovery of insulin, diabetes has changed from an early death sentence to a manageable chronic disease. This change in longevity and duration of diabetes coupled with significant advances in therapeutic options for patients has fundamentally changed the landscape of diabetes management, particularly in patients with type 1 diabetes mellitus. However, hypoglycemia remains a major barrier to achieving optimal glycemic control. Current understanding of the mechanisms of hypoglycemia has expanded to include not only counter-regulatory hormonal responses but also direct changes in brain glucose, fuel sensing, and utilization, as well as changes in neural networks that modulate behavior, mood, and cognition. Different strategies to prevent and treat hypoglycemia have been developed, including educational strategies, new insulin formulations, delivery devices, novel technologies, and pharmacologic targets. This review article will discuss current literature contributing to our understanding of the myriad of factors that lead to the development of clinically meaningful hypoglycemia and review established and novel therapies for the prevention and treatment of hypoglycemia.

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Mini‐review: Glucagon responses in type 1 diabetes – a matter of complexity

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 28 publications

References 53 publications

The Difference in Glucagon Response to Breakfast Between Non-Obese Patients With Long-Duration Type 1 and Type 2 Diabetes

The Difference in Glucagon Response to Breakfast Between Non-Obese Patients With Long-Duration Type 1 and Type 2 Diabetes

Experimentally Induced Hypoglycemia-associated Autonomic Failure in Humans: Determinants, Designs, and Drawbacks

Pathophysiology and management of hypoglycemia in diabetes

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