We are beautifully created with perfectly designed incredibly complex metabolic systems. In the foetus, helpless, entirely at the mercy of our Mother’s habits and well-being our myocardial mitochondria gene expression code for processes that utilize glucose as the sole fuel for our energetics. After birth profound changes in the program gene expression in the myocardial mitochondria occurs, leading to an increase in expression of genes involved in fatty acid metabolism with down regulation of the genes for glucose metabolism.
Intrinsic cardiac cell metabolism in the adult depends primarily on the utilization of fatty acids in beta-oxidation in the mitochondria to produce our ATP (energy). As we corrupt and damage this beautifully delicately balanced process from obesity; metabolic syndrome; myocardial hypertrophy (in hypertension); myocardial ischaemia (from coronary atherosclerosis); cytokine damage (systemic inflammation); oxidative damage & cellular glucotoxicity & lipotoxicity there is a switch back to foetal transcription genes coding for glucose as a fuel rather than fatty acids.
This is associated with altered substrate usage and reduction in mitochondrial ATP generation from glucose metabolism (glycolysis) compared to beta-oxidation of fatty acids thus depleting our important cellular energy. The secondary effect on our cells is triglyceride and free fatty acid (fat) accumulation exacerbating the lipotoxicity with progressive cellular and ultimately myocardial dysfunction.
In the heart this dysfunction gives rise to the well documented heart muscle failure or cardiomyopathy seen particularly in obese subjects with metabolic syndrome and Type 2 Diabetes Mellitus.
Individual Risk Factors for Metabolic Syndrome:
Poor lifestyle choices lead to progressive metabolic chaos and metabolic corruption with the risk of Type 2 Diabetes increasing exponentially as BMI increases above 25 kg/m2. As the metabolic corruption perpetuates in obese subjects specifically with visceral adiposity, insulin resistance and hyperinsulinaemia develops with disastrous knock-on effects on our cellular physiology.
The excessive adipose tissue contributes to chronic increase in circulating fatty acids which in turn corrupt our Insulin signalling pathways exacerbating the Insulin resistance which impairs the metabolism and cellular uptake of glucose and fatty acids.
Excess fatty acids result in increased deposition of fat in the heart, pancreas, muscle and liver (fatty liver) and increased toxic metabolites such as diacylglycerol and ceremide further corrupt cellular energy pathways with toxicity to the various organ systems. Progressive beta-cell dysfunction in the pancreas acting in conjunction with insulin resistance aggravates the hyperglycaemia. The latter contributes to glucotoxicity of metabolic pathways and cellular structures.
Finally the detrimental effects of the adipokines and inflammatory cytokines are additional mechanisms through which obesity potentiates the end organ damage in metabolic syndrome and Type 2 DM.
Thus the high incidence of cardiovascular damage due to obesity; metabolic syndrome and Type 2 Diabetes is multifactorial but chiefly driven at the centre by obesity, metabolic syndrome, insulin resistance, hyperinsulinism and metabolic chaos with lipotoxicity and glucotoxicity.
To reverse and prevent this problem we need to address the central issue of obesity, metabolic syndrome, insulin resistance and Type 2 diabetes mellitus. As you can imagine with the epidemic increase in obesity and overweight status there is a parallel epidemic of obesity and diabetes with increased cardiovascular disease to follow.
Diabetes and obesity are thus closely linked diseases with rising prevalence and incidence in developed and developing countries. Westernized eating habits and lifestyle are presumed to be the major reasons for this epidemic. Official guidelines recommend diets with low-fat contents and high amounts of carbohydrates although it has never been proven that these are effective in reducing cardiovascular disease morbidity and mortality, the major health problems connected with diabetes and obesity.
Recently the Women’s Health Initiative study showed no effect of a diet restricted in fat content and enriched in carbohydrates on cardiovascular morbidity and mortality.
This was a massive trial randomizing >40 000 women to an intervention group eating a low-fat (< 20% of daily calories) and high carbohydrate diet (increased fruit/ vegetables and grains).
Remarkably and surprisingly over 9 years of the study there was no survival benefit in the intervention group taking low-fat high carbohydrate intake.
This study has therefore questioned “conventional wisdom” of the cardiovascular benefits of “low-fat, high carbohydrate” diets.
It seems reducing body weight is considered an important therapeutic intervention to preventing cardiac disease and to treat obese / overweight patients with metabolic syndrome and type 2 diabetes. Most intervention trials have failed to demonstrate a long-lasting diet effect. Putting patients on insulin will often cause an increase in body weight resulting in the need for further insulin to be injected. Although many patients are on high insulin doses, metabolic results are often poor with high HbA1c values (poor diabetic control). The standard low fat-high carbohydrate intervention has been challenged
Historically, there has been a scientific tradition favoring dietary carbohydrate-restriction in obese patients in Europe before the Second World War and in the Fifties in the USA. The recently published A to Z trial showed that the most beneficial effect in weight reduction was in those patients treated with a carbohydrate-restricted diet in comparison with three other dietary interventions, lower in fat and higher in carbohydrates.
There may be individual differences, some patients doing better on a carbohydrate-restricted diet (ATKINS) compared to high carbohydrate diets (Ornish) to reduce weight while others do better on a fat-restricted diet (ZONE and LEARN). A possible explanation might be a different insulin response after a glucose challenge, i.e. a high response reflecting insulin resistance, in those patients that did better on a carbohydrate-restricted diet.
In addition, diets that are rich in carbohydrates will result in an unfavorable cardiovascular risk profile resulting in raised triglycerides and lowered HDL and increased small dense LDL. Glycemic index of carbohydrates is a strong determinant of HDL-cholesterol concentration in plasma. In context of carbohydrate-restriction, dietary saturated fat has also been shown to exhibit a beneficial effect on plasma lipids.These latter conditions are neglected in official recommendations. A recent review of the scientific evidence of dietary carbohydrate-restriction in type 2 diabetes challenged the official recommendation of low-fat diets. The beneficial effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index caloric restricted diet improved metabolic control in patients with type 2 diabetes and also resulted in greater weight loss and reduction or complete cessation of anti-diabetic medications. A two-year randomized trial comparing low carbohydrate diet versus low fat diet in obese patients did also show a more favorable lipid profile in those patients randomized to the low carbohydrate diet treatment.
This study published this year (2012) on very low carbohydrate intake (< 20 g/d) had profound benefit on glucose control (measured by HbA1c level) and weight loss in 35 established Type 2 diabetics on conventional therapy.
This ketogenic diet with low carbohydrate; modest protein and high fat intake gives further “food for thought” to fix a corrupt metabolism.