Into the Heart

Insulin Resistance, metabolic syndrome and high blood pressure

One role of the hormone insulin is to transport glucose to cells to be used as energy. Insulin resistance occurs when the cells do not take in/accept glucose. The glucose then remains in the blood stream and cells have inadequate energy which generates fatigue. Obesity, and excess belly fat are the primary causes of insulin resistance. Obesity, is associated with decreased activity of insulin receptors, a decreased number of insulin receptors and with post-receptor failure to activate tyrosine kinase.

Insulin resistance is the primary disease driver of metabolic syndrome. Several mechanisms connect insulin resistance and metabolic syndrome with hypertension. Data indicates that insulin stimulates renal (kidney) sodium re-absorption. Insulin resistance is also associated with the development of salt-sensitive hypertension through the anti-natriuretic effect of insulin. An anti-natriuretic agent causes the body to retain sodium. Essentially, high insulin levels cause the body to hold salt, which increases blood volume. High blood volume causes the heart and arteries to work harder to push blood through circulatory system. As such, the increase in blood volume contributes to high blood pressure.

High serum insulin levels are also associated with an increase in circulating endothelin-1 in healthy and insulin-resistant individuals. Endothelin-1 is a blood vessel tightening (vasocontrictor) peptide. Elevated levels of endothelin-1 have been demonstrated in various disease conditions that are characterized by sodium retention and/or renal vasoconstriction.

Obesity and excess belly fat stimulate high insulin levels. The high insulin levels then contribute to vasoconstriction, increased intravascular fluid, and decreased vasodilatation, which contribute to the development of hypertension. The good news is that for those with excess weight and/or excess belly fat, weight loss can substantially lessen the bioactive mechanisms that lead to the development of insulin resistance and hypertension.

Sources:

Abnormalities of renal sodium handling in the metabolic syndrome. Results of the Olivetti Heart Study. Strazzullo P, Barbato A, Galletti F
J Hypertens 2006, 24:1633-1639

The underlying mechanisms for the development of hypertension in the metabolic syndrome.
Hidekatsu Yana, Yoshiharu Tomona
Nutrition Journal 2008

Insulin Resistance, sympathetic over activity and high blood pressure

Insulin resistance, increased leptin and free fatty acids levels are thought to be factors that increase sympathetic nervous activation in those with metabolic syndrome. Elevated resting heat rates and baroreflex dysfunction have been reported to play an important role in development of hypertension in metabolic syndrome. Scientific studies indicate that free fatty acids raise blood pressure, heart rate, and α 1-adrenoceptor vasoreactivity, while reducing baroreflex sensitivity, endothelium-dependent vasodilatation, and vascular compliance.

Leptin is a hormone produced by adipocytes (fat cells).Insulin resistance increases leptin levels. Increased leptin levels have been reported to elevate sympathetic nervous system activity suggesting that leptin-dependent sympathetic nervous activation may contribute to obesity associated hypertension.

Catecholamines such as epinephrine & norepinephrine act as hormones or neurotransmitters. They have a powerful effect on blood pressure. Catecholamine concentrations and muscle sympathetic nervous activity are increased in obese individuals as compared with lean individuals. Additionally, muscle sympathetic nervous activity in individuals with central obesity (belly fat) is significantly greater than those in individuals with peripheral obesity (overall body weight).

Keep in mind, for those with excess weight and/or excess belly fat, weight loss can lessen the catecholamine and sympathetic blood vessel tightening (vasoconstriction) mechanisms that can contribute to hypertension.

Sources:
Insulin resistance and the sympathetic nervous system.
Egan BM
Curr Hypertens Rep 2003, 5:247-254

Non-esterified fatty acids and blood pressure elevation: a mechanism for hypertension insubjects with obesity/insulin resistance?
Sarafidis PA, Bakris GL
J Hum Hypertens 2007, 21:12-9.

The underlying mechanisms for the development of hypertension in the metabolic syndrome.
Hidekatsu Yana, Yoshiharu Tomona
Nutrition Journal 2008

Insulin Resistance, oxidative stress and high blood pressure

Metabolic syndrome (high cholesterol, triglycerides, high blood sugar & high blood pressure) is induced by physical inactivity and consumption of a diet high in fat and refined sugar, which generates obesity and excess belly fat. Recent evidence suggest that oxidative stress is elevated in those with metabolic syndrome. Hypertension is associated with oxidative stress, due to nitric oxide inactivation, and down-regulation of nitric oxide synthase isoforms and endothelial nitric oxide activator.

In non-diabetic individuals, lipid peroxidation (oxidized rancid fats), represented by plasma thiobarbituric acid and urinary 8-epi-prostaglandin-F2α , are positively correlated with body mass index and waist circumference. This indicates that fat accumulation is correlated with oxidative stress.

Data from 2,002 non-diabetic subjects of the Framingham Offspring Study showed that systemic oxidative stress is associated with insulin resistance. Insulin resistance induces an impairment in phosphatidylinositol 3-kinase (PI3K) dependent signaling, which in the blood vessels protective lining (the endothelium) may cause imbalance between production of nitric oxide (blood vessel widening molecule) and secretion of endothelin-1 (blood vessel tightening peptide), leading to endothelial dysfunction.

Epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction, which contributes to development of hypertension, and insulin resistance. In a prospective cohort study, each one-unit decrease of flow-mediated dilatation was associated with a significant 16% increase in the relative risk of incident hypertension, suggesting that an impaired endothelial vasomotor function precedes and predicts the future development of hypertension.

Adipose (fat) tissue is a major endocrine organ that secrets a variety of bioactive substances.

Obesity and excess belly fat generate oxidative stress which leads to impaired endothelial function and thus the development of hypertension. Less body fat helps reduce the oxidative stress bioactive mechanisms that contribute to hypertension.

Sources:
Association of oxidative stress, insulin resistance, and diabetes risk phenotypes: the Framingham Offspring Study.
Meigs JB, Larson MG
Diabetes Care 2007, 30:2529-2535

Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms.
Kim JA, Montagnani M, Koh KK, Quon MJ
Circulation 2006, 113:1888-1904

The underlying mechanisms for the development of hypertension in the metabolic syndrome
Hidekatsu Yana, Yoshiharu Tomona
Nutrition Journal 2008