Application of Glucose Clamp Technique in Basic and Clinical Research

About this Research Topic

Background

The incidence of diabetes, obesity, dyslipidemia, hypertension, and metabolic syndrome has increased significantly in recent years and has become a major social problem severely threatening people's health. Existing studies have shown that insulin resistance is a critical potential pathological basis for the occurrence and development of the above metabolic diseases. Thus, investigating the causes behind insulin resistance and the regulation of human metabolic homeostasis will contribute to developing more effective therapies for treating metabolic diseases.

The hyperinsulinemic-euglycemic clamp technique has been recognized as the "gold standard" for assessing insulin sensitivity. Since its introduction by Andres et al. in 1966, the clamp technique has been refined. In addition to insulin sensitivity assessments, the hyperinsulinemic-euglycemic clamp has been widely used for investigating the pharmacodynamic effects of novel anti-diabetic compounds, in particular insulins. Indeed, regulatory agencies require data from glucose clamp studies for new drugs or marketing authorization applications for all new insulin and biosimilar insulin preparations. The pharmacodynamic assessments of novel insulin and insulin analogs are usually combined with pharmacokinetic assessments that provide useful additional information on insulin absorption and elimination. Modern bioassays, often using tandem mass spectrometry combined with liquid chromatography (LC-MS/MS), allow specific determinations of the tested insulin (analog) without the interference of endogenous or other exogenous insulins. This is of particular importance for biosimilar insulins that need to demonstrate both pharmacokinetic and pharmacodynamic bioequivalence to approved reference insulin. The determination of PK/PD parameters in glucose-clamp studies provides valuable information, e.g. on the bioavailability/biopotency, onset, and duration of exposure/action of new insulins allowing unbiased comparisons of the efficacy of different insulin preparations.

Furthermore, the glucose clamp technique may provide additional important information, e.g. on beta-cell function (using hyperglycemic clamps) or hypoglycemia counter-regulation using hypoglycaemic clamp targets. In addition, the pancreatic clamp is used to study the insulin-dependent, glucagon-dependent, or glucose-dependent effects of therapeutic interventions. The combination of the glucose clamp technique with isotope tracers allows further insight into metabolic fluxes in glucose or lipid metabolic pathways.
Because of the increasing importance of metabolic diseases and the high medical need for improved therapies, a special issue will discuss the contributions of the glucose clamp to basic and clinical research in this field as well as to the development of new antidiabetic agents. The main purpose of the papers in this issue is to explore and compile the technological innovation, practical applications, and future developments of the glucose clamp technique. We, therefore, welcome manuscripts on potential future applications and refinements of the clamp technique and the contribution of the glucose clamp to basic and clinical research in diabetes and metabolic diseases.

Potential topics include but are not limited to the following:
• Research status and application progress of clamp technique (update and innovation of clamp technology, quality evaluation, etc.)
• Metabolism-related basic and clinical research based on clamp technology (glucose metabolism, lipid metabolism, energy metabolism, etc.)
• Drug research contributions of the clamp technique
• Discussion on common problems of glucose clamp studies
• Combination of the glucose clamp with other investigational methods

Keywords: clamp technique, metabolism, pharmacodynamics, pharmacokinetics, insulin resistance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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