Affiliation:
1. Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University , 751 85 Uppsala , Sweden
Abstract
Abstract
Context
Insulin-antagonistic, counter-regulatory hormones have been implicated in the development of type 2 diabetes (T2D).
Objective
In this cross-sectional study, we investigated whether glucose-dependent regulation of such hormones differ in individuals with T2D, prediabetes (PD), and normoglycemia (NG).
Methods
Fifty-four individuals with or without T2D underwent one hyperinsulinemic-normoglycemic-hypoglycemic and one hyperglycemic clamp with repeated hormonal measurements. Participants with T2D (n = 19) were compared with a group-matched (age, sex, BMI) subset of participants without diabetes (ND, n = 17), and also with participants with PD (n = 18) and NG (n = 17).
Results
In T2D vs ND, glucagon levels were higher and less suppressed during the hyperglycemic clamp whereas growth hormone (GH) levels were lower during hypoglycemia (P < .05). Augmented ACTH response to hypoglycemia was present in PD vs NG (P < .05), with no further elevation in T2D. In contrast, glucagon and GH alterations were more marked in T2D vs PD (P < .05).
In the full cohort (n = 54), augmented responses of glucagon, cortisol, and ACTH and attenuated responses of GH correlated with adiposity, dysglycemia, and insulin resistance. In multilinear regressions, insulin resistance was the strongest predictor of elevated hypoglycemic responses of glucagon, cortisol, and ACTH. Conversely, fasting glucose and HbA1c were the strongest predictors of low GH levels during hypoglycemia and elevated, i.e. less suppressed glucagon levels during hyperglycemia, respectively. Notably, adiposity measures were also strongly associated with the responses above.
Conclusions
Altered counter-regulatory hormonal responses to glucose variations are observed at different stages of T2D development and may contribute to its progression by promoting insulin resistance and dysglycemia.
Funder
Diabetesfonden
the governmental strategic research program Excellence of Diabetes Research in Sweden
Stiftelsen Familjen Ernfors Fond
P.O. Zetterlings stiftelse
Novo Nordisk Fonden
Agnes och Mac Rudbergs Stiftelse, HORIZON EUROPE Marie-Sklodowska Curie ITN TREATMENT
Uppsala University Hospital ALF grants
Subject
Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism
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