Hyperinsulinemia: A unifying theory of chronic disease?

Abstract

Globally, there is an increasing prevalence of non-communicable diseases. The morbidity and mortality from these conditions confer a greater economic societal burden. Epidemiological research associates insulin resistance in the etiology of these diseases, but there is limited evidence for the mechanism of damage. Emerging research suggests that hyperinsulinemia, a symptom of insulin resistance, may cause these pathological changes, and therefore be an independent contributor to these diseases. This review shows that hyperinsulinemia, or excessive insulin secretion, should be considered independently to insulin resistance, defined as glucose uptake rate, even though the two conditions are intertwined and will co-exist under normal conditions. Hyperinsulinemia directly and indirectly contributes to a vast array of metabolic diseases including all inflammatory conditions, all vascular diseases, gestational and type 2 diabetes, non-alcoholic fatty liver disease, obesity and certain cancers and dementias. The mechanisms include increased production of: insulin growth factor-1; reactive oxidative species and advanced glycation end-products; and triglyceride and fatty acids. Hyperinsulinemia also directly and indirectly affects many other hormones and cytokine mechanisms including leptin, adiponectin and estrogen. There is limited research standardizing the hyperinsulinemia diagnostic process. Methodological concerns and lack of standardized reference ranges preclude the use of fasting insulin. Most research has also focused on insulin resistance and it is unknown whether these methods translate to hyperinsulinemia.

A low-carbohydrate survey: Evidence for sustainable metabolic syndrome reversal

“…However, while obesity is highly correlated with the condition, we (and others) suggest that it is the expansion of adipose stores beyond a person's individual storage capacity, 25,26 driven by and in conjunction with hyperinsulinaemia because of the overconsumption of processed dietary carbohydrates in the setting of a Western diet -so prevalent in modern society -that drives this disease process. 26,27,28 Inflammation, especially the presence of pro-inflammatory macrophages in fat stores, such as the visceral adipose tissue, is another key marker of the developing pathology. 25,29 The inflamed adipose tissue appears to lose its ability to properly respond to insulin, resulting in loss of its capacity to protectively buffer fatty acids (including sugars and starches converted to fatty acids via de novo lipogenesis to be 'safely' stored).…”

Sleep architecture, insulin resistance and the nasal cycle: Implications for positive airway pressure therapy

“…Population studies demonstrate that elevations are an early marker of metabolic disease. 2 Hyperinsulinaemia is a common aetiological factor for many metabolic diseases, especially type 2 diabetes, macro-and microvascular disease, certain cancers and dementias. Recent research suggests that hyperinsulinaemia may be present in a significant proportion of the population with both normal body mass indices and normal glucose tolerances, 6 a clinically silent harbinger of the subsequent development of type 2 diabetes over 5-10 years.…”

“…This metabolic theory of obesity is strengthened by the recognition of impaired insulin homeostasis and hyperinsulinaemia being a recognised risk factor for metabolic disease. 2 Emerging research suggests that hyperinsulinaemia precedes the development of both obesity and insulin resistance. 1,3,4 Therefore, understanding the causes, and management, of hyperinsulinaemia may elicit novel ways of managing metabolic disease.…”

A 12-week low-carbohydrate, high-fat diet improves metabolic health outcomes over a control diet in a randomised controlled trial with overweight defence force personnel

“…In particular, it is the postprandial insulin surge and its consistent elevation following a high-carbohydrate load that is problematic, particularly for populations with insulin resistance. Consistently elevated levels of insulin, or hyperinsulinaemia, not only makes for a challenging body fat burning environment, but also has been shown to play a causal role in chronic diseases such as metabolic syndrome, diabetes, and cardiovascular disease (Crofts et al 2015).…”