Prezentare Adipozopatie Anca 3 Martie 2015 [Compatibility Mode]

ADIPOSOPATHY:CLINICAL PATHOPHYSIOLOGY

MULTIPLE CHALLENGES

Summary from Obesity Congress 2014 & NCDs Congress 2015By dr Anca Hancu

Areas to cover

CLINICAL PATHOPHYSIOLOGY THE MULTIPLE CHALLENGES CONCLUSIONS

Harold Bays, Adiposopathy, Sick Fat, Ockhams Razor; and Resolution of the Obesity Paradox, Curr Atheroscler Rep. 2014 May;16(5):409

Adiposopathy (sick fat) is defined as adipocyte/adipose tissuedysfunction caused by positive caloric balance and sedentary lifestyle in genetically and environmentally susceptible individuals.

Among competing theories , the hypothesis with the fewest assumptionsis the one best selected.

Ockhams razor supports adiposopathy as the primary cause of mostcases of adiposity-related metabolic diseases, which in turn helps resolvethe obesity paradox.

Adiposopathy (sick fat)

Adiposopathy and sick fat are scientific and clinical terms, respectively, that simultaneously emerged towards better aligning thescientific findings of researchers with the patient care experience of clinicians

These terms recognized the pathogenic potential of an increasedamount of body fat as a primary contributor to metabolic disease andincreased CVD risk

Adiposopathy (sick fat)


Immune cells modulation in adipose tissue during obesity

H.L. Kammoun et al., Adipose tissue inflammation in glucose metabolism, Rev Endocr Metab Disord (2014) 15:31-44

Adipose tissue inflammation in pathogenesis of metabolic syndrome and type 2 diabetes

Nathalie Esser et al., Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes, Diabetes Research and Clinical Practice 2014 Aug;105(2): 141-150

Obesity as a disease


Pathogenesis of type 2 diabetes, insulin resistance andbeta cell dysfunction

Caroline Day, Bailey J. C., Obesity in the pathogenesis of type 2 diabetes The British Journal of Diabetes & Vascular Disease, March/Aprilie 2014, vol 11(2); 55-61.

Molecular Mechanisms of Lipid-Induced Hepatic Insulin Resistance

ShulmanGI. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Caediometabolic Disease. N Engl J Med 371;12

Mechanism by which Selective Insulin Resistance in Skeletal MuscleLeads to Atherogenic Dyslipidemia and Nonalcoholic Fatty Liver

Disease

ShulmanGI. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Caediometabolic Disease. N Engl J Med 371;12

HE Bays. J Am Coll Cardiol 2011;57:246173

Who is the person with type 2 diabetes mellitus and

atherogenic dyslipidemia?

High glucose blood levels(prediabetes, type 2 diabetes mellitus)

Insulin resistance

High blood pressure

Adiposopathic dyslipidemia

o Increased triglyceride, triglyceride rich lipoprotein, and lipoproteinremnant levels

o Decreased high density lipoprotein cholesterol levelso Increased atherogenic particle number (i.e increased apolipoprotein B)o Increased small dense low density lipoprotein particles


Clinical importance

Harold Bays et al., Adiposopathy, Sick Fat, Ockhams Razor; and Resolution of the Obesity Paradox, Curr Atheroscler Rep. 2014 May;16(5):409

Metabolic syndrome Atherosclerosis Fatty liver Hypoandrogenemia in men Hypoandrogenemia in

women Polycystic ovarian

syndrome, menstrual disorders, and infertility

Hyperuricemia Cholelithiasis Glomerulopathy Prothrombotic state Cancer Other inflammatory

diseases (e.g. worseningdepression, asthma, osteoarthritis)

Clinical importance

Selected biomarkers of adiposopathy

Harold E. Bays et al., Obesity, adiposity, and dyslipidemia: A consensus statement from the national lipid association, Journal of Clinical Lipidology (2013) 7, 304-383

Definition of MHO phenotype MHO phenotype may exist in the absence of metabolic abnormalities

As there is no standard metabolic health definition different inclusion criteria and/or cut-offs have been used to discrimate metabolically healthy from metabolicallyunhealthy subjects thus making comparisons betweeen studies difficult

There is considerable variability in MHO prevalence according to which set of criteriaare used to define metabolic health

Phillips CM., Metabolically healthy obesity: Definition, determinants and clinical implications, Rev Endocr Metab Disord. 2013 Sep;14(3):219-27

Heterogeneity of obesityMetabolically healthy obesity (MHO)

It has been suggested that the MHO phenotype starts in childhood andpersists into adulthood

Whether the metabolic health status of obese individuals transitionsbetween healthy and unhealthy states over time is unclear, but it mayaccount for the observed decreasing MHO prevalence with age

Previous prospective studies have considered the MHO phenotype as a static condition

However it is possible that transition between MHO and MUO (metabolically unhealthy obese) over the follow up period, as well as a lack of a unique MHO definition and different follow-up times, mayaccount for conflictiong findings regards CVD and mortality outcomes


Metabolically healthy obesity (MHO)

Clinical implications of MHO


Current obesity treatment guidelines do not distinguish between MHO and MUO subjects, and recommended weight loss for all obeseindividuals, starting with lifestyle intervention

There is no suggestion that MHO individuals should not be treated, but stratification of obese individuals based on their metabolic healthphenotype may be important in the early identification of those whoshould be prioritised for pharmacological and lifestyle intervention andin determining the most appropiate therapeutic strategy

However to date few studies have examined the impact of dietary andexercise interventions in MHO and have produced conflictings results

Adiposopathy: a new clinical and pathogenic concept

Heterogeneity and the paradox of obesity, represent a serious challenge both for the practicians and scientists

Conclusions

The challenges for scientists (5)

When will the personalized treatment be available

for each person?

N.Hancu, C. Nita. 2013

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