Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction

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Abstract

Hyperinsulinemia is strongly associated with type 2 diabetes. Racial and ethnic minority populations are disproportionately affected by diabetes and obesity-related complications. This mini-review provides an overview of the genetic and environmental factors associated with hyperinsulinemia with a focus on racial and ethnic differences and its metabolic consequences. The data used in this narrative review were collected through research in PubMed and reference review of relevant retrieved articles. Insulin secretion and clearance are regulated processes that influence the development and progression of hyperinsulinemia. Environmental, genetic, and dietary factors are associated with hyperinsulinemia. Certain pharmacotherapies for obesity and bariatric surgery are effective at mitigating hyperinsulinemia and are associated with improved metabolic health. Hyperinsulinemia is associated with many environmental and genetic factors that interact with a wide network of hormones. Recent studies have advanced our understanding of the factors affecting insulin secretion and clearance. Further basic and translational work on hyperinsulinemia may allow for earlier and more personalized treatments for obesity and metabolic diseases.

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Glucose clamp technique: a method for quantifying insulin secretion and resistance.

Christian R. Andres, Stephanie J. Tobin, R. DeFronzo (1979)

Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.

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Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans.

Kimber L. Stanhope, Jean Schwarz, Nancy Keim … (2009)

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle-triglyceride and -cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.

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Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.

C Weyer, T. Funahashi, S. Tanaka … (2001)

Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.

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Author and article information

Contributors

Caroline M Apovian:

ORCID: http://orcid.org/0000-0002-8029-1922

Journal

Journal ID (nlm-ta): J Endocr Soc

Journal ID (iso-abbrev): J Endocr Soc

Journal ID (publisher-id): jes

Title: Journal of the Endocrine Society

Publisher: Endocrine Society (Washington, DC )

ISSN (Electronic): 2472-1972

Publication date Collection: 01 September 2019

Publication date (Electronic): 24 July 2019

Volume: 3

Issue: 9

Pages: 1727-1747

Affiliations

[1] Department of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University School of Medicine and Boston Medical Center , Boston, Massachusetts

Author notes

Correspondence: Caroline M. Apovian, MD, Boston University School of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston Medical Center, 720 Harrison Avenue, 8th floor, Suite 8100, Boston, Massachusetts 02118. E-mail: caroline.apovian@ 123456bmc.org .

Author information

Dylan D Thomas http://orcid.org/0000-0002-8838-2992

Barbara E Corkey http://orcid.org/0000-0002-5467-1630

Nawfal W Istfan http://orcid.org/0000-0001-7163-8309

Caroline M Apovian http://orcid.org/0000-0002-8029-1922

Article

Publisher ID: 201900065

DOI: 10.1210/js.2019-00065

PMC ID: 6735759

PubMed ID: 31528832

SO-VID: 59a2ab1b-fe0b-4543-85e1-d9c5e2a5a79b

License:

This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 13 February 2019

Date accepted : 18 July 2019

Page count

Pages: 21

Funding

Funded by: National Institute of Diabetes and Digestive and Kidney Diseases 10.13039/100000062

Award ID: P30DK046200

Award ID: T32DK007201

Funded by: National Center for Advancing Translational Sciences 10.13039/100006108

Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction

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GLUT4 biology

Most cited references 164

Glucose clamp technique: a method for quantifying insulin secretion and resistance.

Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans.

Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.

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