There is a well-established link between central obesity, metabolic syndrome, type 2 diabetes is significantly increased (American Diabetes Association et al. What is really needed for the pandemic of obesity, the metabolic syndrome (MS), and Its precise definition varies slightly between guidelines issued by expert the American Diabetes Association (ADA) criteria for impaired fasting glucose. THE RELATIONSHIP BETWEEN OBESITY, GLYCEMIA AND LEPTIN leptin level of 2 type diabetes mellitus patients with metabolic syndrome. . The selection of patients with metabolic syndrome was based no the criteria.
FAAH and MGL activities in obese humans were not correlated with blood pressure, skinfold thicknesses, fasting glucose, insulin, HbA1c, triglycerides or cholesterol levels. Conclusions FAAH in adipocytes is differentially altered in animal models of obesity and diabetes, while MGL activity is increased by both.
However, in obese humans, FAAH or MGL activity in adipocytes is not affected by diabetes, dyslipidaemia or other markers of metabolic dysfunction.
This suggests increased circulating levels of endocannabinoids are not a result of altered degradation in adipose tissue.
The ECS is comprised of endocannabinoid ligands, their receptors, and the enzymes required for their synthesis and degradation. N-arachidonoylethanolamide anandamide, AEA [ 5 ] and 2-arachidonoylglycerol 2-AG [ 67 ] are the two best characterised endocannabinoids, and the enzymes which degrade them are predominantly fatty acid amide hydrolase FAAH and monoacylglycerol lipase MGL respectively [ 89 ].
It has been suggested that the ECS is upregulated in human obesity on the basis that plasma concentrations of AEA [ 1011 ], 2-AG [ 12 ] and other acyl-ethanolamides [ 13 ] correlate positively with body mass index BMI. Concept of glucose metabolism disorder American Diabetes Association criteria Few brief pointers are provided. Obesity is a risk factor for atherosclerosis due to a variety of mechanisms which are summarized in Figure 2.
Insulin resistance, which is the common link with MS, leads to glucose metabolism disorders, dyslipidemia, high blood pressure, endothelial dysfunction, and inflammation induced by cytokine imbalance. The latter, ie an excess of harmful cytokines interleukins 6 and 18, tumor necrosis factor alpha, and leptin being among the most important combined with a scarcity of protector cytokines adiponectin. Diagram of atherosclerosis pathogenesis in obesity.
The three main mechanisms are insulin resistance, increased free fatty acids, and cytokine imbalance. The large quantity of non-sterified fatty acids reduces the use of glucose by skeletal muscle, stimulates the hepatic production of very low-density lipoproteins and glucose, and propitiates the acute secretion of insulin.
The lipotoxic effect in the pancreatic beta cells caused by free fatty acids over the long term could be part of the connection between obesity, insulin resistance, and the development of DM2.
Understanding the link between obesity and diabetes
However, the portal theory has been placed in quarantine and there is some evidence that it is unable to explain, by itself, all of the metabolic anomalies present in abdominally obese individuals.
In the first place, epidemiological studies have demonstrated that the degree of risk involved when multiple risk factors are present is greater than the sum of the risks attributable to each individual factor; in other words, under these circumstances, risk increases geometrically rather than linearly. In the second place, the algorithms habitually used to calculate cardiovascular risk do not include several metabolic factors which have been shown to independently increase the risk of vascular complications.
These include the prothrombotic state, inflammatory status, and hypertriglyceridemia. The additional risk associated with these factors exceeds that attributed to conventional risk factors.
Understanding the link between obesity and diabetes
In the third place, some of the risk attributed to conventional factors probably derives from factors which have not been considered or measured. Finally, as MS progresses and often culminates in DM2, the risks associated with the latter should be added to those already mentioned.
The evolution of MS in terms of its pathological consequences are shown in Figure 3. Evolution and pathology of the metabolic syndrome adapted from Haslam et al Figure 4 summarizes the latest theories regarding the relationship between obesity and MS, which is posited as a dysfunction of adipose tissue with insulin resistance appearing later when compensatory response mechanisms have been exhausted.
Metabolic syndrome as a dysfunction of adipose tissue adapted from Laclaustra et al From what has been described here, it is clear that MS is a first order risk factor for atherothrombotic complications. Its presence or absence should therefore be considered an indicator of long-term risk.
These include coronary heart disease and stroke as the main complications, although peripheral arterial disease is also common and tends to be more serious higher indices of serious ischemia and amputations when it is cause by diabetes than when it is caused by other mechanisms.
Micro- and macroangiopathy exist side by side and their harmful effects are multiplied in DM2. Damage to the endothelium produced by accumulation of glucosilation sub-products, reduced production of nitric oxide, and endothelial inflammation are among the most characteristic mechanisms involved in the process. These changes have led to the alarming increase in incidence of diabetes and obesity. After adjusting by age, the largest increases in waist circumference were observed in the youngest age group years.
Over the past 20 years, prevalence rates for obesity have tripled in developing countries which have adopted western lifestyles.
These have shown the typical patterns of reduced physical activity and over consumption of high energy-density meals. There have been several studies into the prevalence of obesity in the Spanish general population.
One of the reasons for the current interest in MS is its high prevalence. Prevalence of metabolic syndrome in the MESYAS23 register by age and gender in 18 healthy members of the working population.
Obesity, Metabolic Syndrome and Diabetes: Cardiovascular Implications and Therapy
Finally, the DM2 epidemic is expanding principally in developed and developing countries. Estimates are not very encouraging and have taken public health authorities by surprise.
The functional value of this adipose tissue hormone in the physiological reactions of the body is very complicated. Leptin is a multifunctional hormone of adipose tissue which intensifies glyconeogenesis processes of the liver and absorbing glucose by the skeletal muscles, as well as influencing speed of lipolysis, reducing the amount of triglycerides in white adipose tissue, and enhancing thermogenesis.
Interestingly, it decreases the amount of triglycerides in the liver, pancreas and skeletal muscles without increasing the level of free fatty acids in the plasma. Leptin stimulates the central nervous system regulates the saturation centerproduces modulating effect on the development of atherosclerosis and arterial pressure [5, 6, 7].
Today, there are known environmental factors that influence the leptin level even more than the genetic component. In particular, scientific literature describes that smoking is accompanied by the development of hyperadrenergic state which contributes to lowering the level of leptin . Thus, infectious diseases, endotoxins and cytokines lead to cause hyperleptinemia. Glucocorticoids, sex steroids testosteroneand thyroid hormones play a significant role in the interaction between leptin and receptors, which correspondently contributes to the development of the resistance to leptin at the central nervous system level.
According to the scientific data, patients with de novo type 1 diabetes mellitus possess low leptin level, but it gradually increases after insulin therapy prescritpion.
However, patients with type 2 diabetes mellitus and signs of insulin resistance are marked with the elevated leptin level in fasting state. Consequently, the lower the insulin sensitivity, the higher the leptin level, and this is the main criterion of hyperleptinemia being an integral part of the metabolic syndrome. Due to present-day beliefs, obesity is accompanied by a high endogenous leptin level and exogenous leptin resistance. Many scientific studies prove that the lipotoxic effects of free fatty acids and the adipocytes imbalance may be caused by obesity and insulin resistance progression.
It is also known that cortisol stimulates the synthesis of cortisol-dependent lipoprotein lipase produced on the upper body adipocytes capillaries, anterior abdominal wall and visceral adipose tissue which leads to the abdominal obesity progression [1, 2].
As a result, leptin resistance is one of the leading etiopathogenetic factors in the development and progression of metabolic syndrome. By this time, the study of the leptin effect on arterial hypertension and insulin resistance of adults has been carrying on. The aim To investigate the relationship between the leptin level and the degree of obesity and insulin resistance of type 2 diabetes mellitus patients with metabolic syndrome.
Materials and methods 79 males with type 2 diabetes mellitus and metabolic syndrom were examined. The first group included 48 patients who took Metformin and the second one — 31 persons taking Metformin, Glimepiride of one-day functioning and Thiazolidinediones pioglitazone.
The age of patients was years and older. The control group consisted of 23 overweight patients without diabetes mellitus and metabolic syndrome. Three out of five indicators make it possible to diagnose metabolic syndrome. According to the protocol, the patients were examined for their waistline, body mass index BMIglucose level, and glycohemoglobin.
Triglycerides and leptin level were additionalyy determined in blood serum. The study has been conducted in dynamics: All patients were recommended to modify their lifestyle: In determining glycemia levels, it has been found out that in the first group, the average glycemic index at the primary examination was 8. Moreover, in this group, the level of glycemia to 7.