MANIFESTATIONS AND MECHANISMS OF DEVELOPMENT OF SYNDROME X

1167

ResearchBib IF - 11.01, ISSN: 3030-3753, Volume 2 Issue 3

MANIFESTATIONS AND MECHANISMS OF DEVELOPMENT OF SYNDROME X

Panjiyev Jonibek Abdumajidovich

Department of Fundamental Medical Sciences of the Asian International University.

Bukhara, Uzbekistan.

https://doi.org/10.5281/zenodo.15070444

Abstract.

Metabolic syndrome, characterized by a constellation of metabolic

abnormalities, including central obesity, insulin resistance, hypertension, and dyslipidemia,

poses a significant risk for the development of atherosclerotic cardiovascular diseases and type

II diabetes mellitus. The diagnosis of metabolic syndrome necessitates the presence of 3 or more

of these metabolic abnormalities, signaling an urgent need for proactive identification and

intervention strategies.

The prevalence of MetS is rapidly increasing worldwide, largely as a

consequence of the ongoing obesity epidemic. Environmental factors during periods early in

development have been shown to influence the susceptibility to develop disease in later life. In

particular, there is a wealth of evidence from both epidemiological and animal studies for

greater incidence of features of MetS as a result of unbalanced maternal nutrition. The

mechanisms by which nutritional insults during a period of developmental plasticity result in a

MetS phenotype are now beginning to receive considerable scientific interest.

Keywords:

insulin resistance, metabolic syndrome, type II diabetes mellitus,

hypertension, atherogenic dyslipidemia

ПРОЯВЛЕНИЯ И МЕХАНИЗМЫ РАЗВИТИЯ СИНДРОМА X

Аннотация.

Метаболический синдром, характеризующийся совокупностью

метаболических нарушений, включая центральное ожирение, резистентность к инсулину,

гипертонию

и

дислипидемию,

представляет

значительный

риск

развития

атеросклеротических сердечно-сосудистых заболеваний и сахарного диабета II типа.

Диагноз метаболического синдрома требует наличия 3 или более из этих метаболических

нарушений, что свидетельствует о срочной необходимости упреждающих стратегий

выявления и вмешательства. Распространенность МС быстро растет во всем мире, в

основном из-за продолжающейся эпидемии ожирения. Было показано, что факторы

окружающей среды в периоды раннего развития влияют на восприимчивость к развитию

заболевания в более позднем возрасте. В частности, имеется множество доказательств

как эпидемиологических, так и животных исследований о большей частоте признаков

МС в результате несбалансированного питания матери. Механизмы, посредством

которых пищевые нарушения в период пластичности развития приводят к фенотипу МС,

в настоящее время начинают привлекать значительный научный интерес.

1168

ResearchBib IF - 11.01, ISSN: 3030-3753, Volume 2 Issue 3

Ключевые слова:

резистентность к инсулину, метаболический синдром, сахарный

диабет II типа, гипертония, атерогенная дислипидемия.

Metabolic syndrome is an accumulation of several disorders that raise the risk of

atherosclerotic cardiovascular disease, including myocardial infarction, cerebrovascular

accidents, peripheral vascular diseases, insulin resistance, and type II diabetes mellitus. The

cluster of metabolic disorders that define metabolic syndrome includes central obesity, insulin

resistance, hypertension, and atherogenic dyslipidemia.

Evolution of the criteria or the metabolic syndrome since the original definition by the

World Health Organization in 1998 reflects growing clinical evidence and analysis by a variety

of consensus conferences and professional organizations. The major features of the metabolic

syndrome include central obesity, hypertriglyceridemia, low levels of high-density lipoprotein

(HDL) cholesterol, hyperglycemia, and hypertension.

The most challenging feature of the metabolic syndrome to de ne is waist circumference.

Intraabdominal circumference (visceral adipose tissue) is considered most strongly related to

insulin resistance and risk of diabetes and CVD, and or any given waist circumference the

distribution of adipose tissue between SC and visceral depots varies substantially. Thus, within

and between populations, there is a lesser vs. greater risk at the same waist circumference. These

differences in populations are reflected in the range of waist circumferences considered to confer

risk in different geographic locations. The prevalence of the metabolic syndrome varies around

the world, in part reflecting the age and ethnicity o the populations studied and the diagnostic

criteria applied. In general, the prevalence of the metabolic syndrome increases with age. The

global incidence of metabolic syndrome rises almost parallel to the incidence of obesity.

According to the National Health and Nutrition Examination Survey (NHNES), the

prevalence of metabolic syndrome in adults increased from 25.3% to 34.2% in 2012.

RISK FACTORS:

Overweight/Obesity

Although the metabolic syndrome was first described in the early twentieth century, the

worldwide overweight/ obesity epidemic has recently been the force driving its increasing

recognition. Central adiposity is a key feature of the syndrome, and the syndrome’s prevalence

reflects the strong relationship between waist circumference and increasing adiposity.

However, despite the importance of obesity, patients who are o normal weight may also

be insulin resistant and may have the metabolic syndrome.

Sedentary lifestyle

1169

ResearchBib IF - 11.01, ISSN: 3030-3753, Volume 2 Issue 3

Physical inactivity is a predictor of CVD events and the related risk of death. Many

components of the metabolic syndrome are associated with a sedentary lifestyle, including

increased adipose tissue (predominantly central), reduced HDL cholesterol, and increased

triglycerides, blood pressure, and glucose in genetically susceptible persons. Compared with

individuals who watch television or videos or use the computer 4 h daily have a two- old

increased risk of the metabolic syndrome.

Aging

The metabolic syndrome affects nearly 50% of the U.S. population older than age 50, and

at >60 years of age women are more often affected than men. The age dependency of the

syndrome’s prevalence is seen in most populations around the world.

Diabetes mellitus

Diabetes mellitus is included in both the NCEP and the harmonizing definitions of the

metabolic syndrome. It is estimated that the great majority (~75%) of patients with type 2

diabetes or impaired glucose tolerance have the metabolic syndrome. T e presence of the

metabolic syndrome in these populations relates to a higher prevalence of CVD than in patients

who have type 2 diabetes or impaired glucose tolerance but do not have this syndrome.

Cardiovascular disease

Individuals with the metabolic syndrome are twice as likely to die of cardiovascular

disease as those who do not, and their risk of an acute myocardial infarction or stroke is three old

higher. The approximate prevalence of the metabolic syndrome among patients with coronary

heart disease (CHD) is 50%, with a prevalence of ~35% among patients with premature coronary

artery disease (be ore or at age 45) and a particularly high prevalence among women. With

appropriate cardiac rehabilitation and changes in lifestyle (e.g., nutrition, physical activity,

weight reduction, and—in some cases—pharmacologic therapy), the prevalence of the syndrome

can be reduced.

Lipodystrophy

Lipodystrophic disorders in general are associated with the metabolic syndrome. Both

genetic lipodystrophy (e.g., Berardinelli-Seip congenital lipodystrophy, Dunnigan amilial partial

lipodystrophy) and acquired lipodystrophy (e.g., HIV-related lipodystrophy in patients receiving

antiretroviral therapy) may give rise to severe insulin resistance and many of the components of

the metabolic syndrome.

Pathophysiology:

Metabolic syndrome has been studied extensively over the past few decades. Insulin

resistance, adipose tissue dysfunction, and chronic inflammation have been proposed as the basic

components of the pathogenesis of metabolic syndrome.

1170

ResearchBib IF - 11.01, ISSN: 3030-3753, Volume 2 Issue 3

Under normal circumstances, a sudden rise in serum glucose level triggers insulin

secretion from the pancreatic β-cells, which promote cellular glucose uptake via glucose

transporters. However, in those with insulin resistance, tissues are less sensitive to this acute rise

in insulin, resulting in a higher serum glucose level and hyperinsulinemia. The impairment in

insulin secretion and abnormal insulin signaling results in impaired glucose metabolism, fat

deposition, cardiotoxicity, and chronic inflammation, the characteristic features of metabolic

syndrome.

Visceral obesity is another essential component of metabolic syndrome. Free fatty acids

released by the adipose tissues promote insulin resistance and inhibit insulin secretion from the

pancreatic beta cells. The high-free fatty acids inhibit glucose uptake in skeletal muscles and

increase hepatic gluconeogenesis and lipid synthesis by inducing protein kinases. Both insulin

resistance and free fatty acids play a major role in the pathogenesis of hypertension,

prothrombotic state, and chronic inflammation. Visceral adipose tissues also secrete multiple

active metabolites and various pro-inflammatory cytokines, C-reactive protein, leptin, and

resistin, which induce chronic inflammation, a possible mechanism of various complications of

metabolic syndrome.

The inflammatory cytokines further increase insulin resistance in skeletal muscles, liver,

and adipose tissues by inhibiting the insulin signaling pathway in these tissues. These cytokines,

especially tumor necrosis factor-alpha, promote insulin resistance by inactivating insulin

receptors in the skeletal muscles. Insulin resistance further activates inflammatory cytokines and

promotes thrombogenesis by increasing the fibrinogen level.

Metabolic syndrome adversely influences several div systems. Insulin resistance causes

microvascular damage, predisposing patients to endothelial dysfunction, vascular resistance,

hypertension, and vessel wall inflammation. Endothelial damage can impact the div’s

homeostasis, causing atherosclerotic disease and the development of hypertension. Furthermore,

hypertension adversely affects several div functions, including increased vascular resistance

and stiffness, causing peripheral vascular disease, structural heart disease comprising of left

ventricular hypertrophy and cardiomyopathy, and leading to renal impairment.

Accumulated effects of endothelial dysfunction and hypertension due to metabolic

syndrome can further result in ischemic heart disease. Endothelial dysfunction due to increased

levels of plasminogen activator inhibitor-1 and adipokine levels can cause thrombogenicity,

while hypertension causes vascular resistance by which coronary artery disease can develop.

Dyslipidemia associated with metabolic syndrome can drive the atherosclerotic process,

leading to symptomatic ischemic heart disease.

1171

ResearchBib IF - 11.01, ISSN: 3030-3753, Volume 2 Issue 3

Conclusion:

The metabolic syndrome (syndrome X, insulin resistance syndrome)

consists of a constellation o metabolic abnormalities that confer increased risk of cardiovascular

disease (CVD) and diabetes mellitus.

The growing prevalence of metabolic disease challenges

biological researchers to elucidate the mechanisms involved in the etiology and the pathogenesis

of MetS and its associated features. Evidently, the disease itself and the mechanisms leading to

its onset are multi-factorial. However, exposure to an inappropriate diet during the

developmental period clearly plays a role in exacerbating the risk of disease onset.

REFERENCES

1.

Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease

2.

Grundy SM. Metabolic syndrome: therapeutic considerations

3.

Ferrannini E. Metabolic syndrome: a solution in search of a problem

4.

Campion J, Milagro FI, Martinez JA. Individuality and epigenetics in obesity

5.

Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty

phenotype hypothesis

Diabetologia., 35 (1992), pp. 595-601

6.

Godfrey KM. Maternal regulation of fetal development and health in adult life

7.

Samson SL, Garber AJ. Metabolic syndrome. Endocrinol Metab Clin North Am. 2014

Mar;43(1):1-23. [

PubMed

]

8.

Kazemi T, Sharifzadeh G, Zarban A, Fesharakinia A. Comparison of components of

metabolic syndrome in premature myocardial infarction in an Iranian population: a case -

control study. Int J Prev Med. 2013 Jan;4(1):110- [

PMC free article

] [

PubMed

]

9.

Pucci G, Alcidi R, Tap L, Battista F, Mattace-Raso F, Schillaci G. Sex- and gender-

related prevalence, cardiovascular risk and therapeutic approach in metabolic syndrome:

A review of the literature. Pharmacol Res. 2017 Jun;120:34-42. [

PubMed

]

10.

Caballero B. Humans against Obesity: Who Will Win? Adv Nutr. 2019 Jan

01;10(suppl_1): S4-S9. [

PMC free article

] [

PubMed

]

11.

Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic

disease. J Clin Invest. 2017 Jan 03;127(1):1-4. [

PMC free article

] [

PubMed

]

12.

Matsuzawa Y, Funahashi T, Nakamura T. The concept of metabolic syndrome:

contribution of visceral fat accumulation and its molecular mechanism. J Atheroscler

Thromb. 2011;18(8):629-39. [

PubMed

]

13.

Handelsman Y. Metabolic syndrome pathophysiology and clinical presentation. Toxicol

Pathol. 2009 Jan;37(1):18-20. [

PubMed

]

14.

van der Pal KC, Koopman ADM, Lakerveld J, van der Heijden AA, Elders PJ, Beulens

JW, Rutters F. The association between multiple sleep-related characteristics and the

1172

ResearchBib IF - 11.01, ISSN: 3030-3753, Volume 2 Issue 3

metabolic syndrome in the general population: the New Hoorn study. Sleep Med. 2018

Dec; 52:51-57. [

PubMed

]

15.

Kim JY, Yi ES. Analysis of the relationship between physical activity and metabolic

syndrome risk factors in adults with intellectual disabilities. J Exerc Rehabil. 2018

Aug;14(4):592-597. [

PMC free article

] [

PubMed

]

16.

Xu H, Li X, Adams H, Kubena K, Guo S. Etiology of Metabolic Syndrome and Dietary

Intervention. Int J Mol Sci. 2018 Dec 31;20(1) [

PMC free article

] [

PubMed

]

17.

Gluvic Z, Zaric B, Resanovic I, Obradovic M, Mitrovic A, Radak D, Isenovic ER. Link

between

Metabolic

Syndrome

and

Insulin

Resistance. Curr

Vasc

Pharmacol. 2017;15(1):30-39. [

PubMed

]

18.

Fahed G, Aoun L, Bou Zerdan M, Allam S, Bou Zerdan M, Bouferraa Y, Assi HI.

Metabolic Syndrome: Updates on Pathophysiology and Management in 2021. Int J Mol

Sci. 2022 Jan 12;23(2) [

PMC free article

] [

PubMed

]