This document discusses the relationship between adiposity, insulin resistance, and gout. It states that obesity leads to chronic low-grade inflammation in adipose tissue, contributing to insulin resistance. Insulin resistance then causes hyperinsulinemia, inhibiting urate excretion by the kidneys and leading to hyperuricemia and gout. Metabolic syndrome, which includes insulin resistance, is also linked to higher uric acid levels and prevalence of gout. The conclusion is that adiposity can lead to insulin resistance, hyperinsulinemia, hyperuricemia due to inhibited urate excretion, and ultimately gout.

1. ADIPOSITY, INSULIN
RESISTANCE AND GOUT

2. ADIPOSITY AND GOUT
 Obesity –excessive accumulation of body fat(adipose tissue)
 Obesity is associated with a state of chronic low grade inflammation that
contributes to insulin resistance, type 2 diabetes and increased risk of
hyperuricemia and gout.
 Inflammatory cells accumulate in adipose tissue with increasing body weight
and evidence in mounting that implicates this inflammatory cell as significant
contributors to obesity associated insulin resistance.
 Although the pathogenesis of insulin resistance in obesity Is multifactorial,
there is evidence that adipose tissue macrophages with chronic, low grade
inflammation are a major contributor.
 Furthermore, many regulators play a critical role in obesity by regulating
macrophage recruitment such as c-cmotit chemokine receptor 5 (CCRS);
phosphoinositide-3-kinase, dendritic cells, and adipose tissue size.

3.  Inflammatory mediators in adipose tissue has been shown
to cause insulin resistance in adipocytes e.g. TNF-α
treated adipocytes exhibited decreased insulin signaling
and subsequently decreased glucose up take.
 It is suggested that insulin resistance may be a mediator
between adiposity and hyperuricemia (gout) as insulin
excretion may be exacerbated by adipocytes and insulin
has been identified as cause of hyperuricemia by
exhibiting uric acid formation.

4. INSULINE RESISTANCE AND GOUT.
 Hyperuricemia and metabolic syndrome.
 metabolic syndrome is currently defined as having at
least 3-5 signs (abdominal obesity, impaired fasting
glucose, hypertriglyceridemia, low HDL cholesterol and
elevated blood pressure.
 In patients with manifest atherosclerosis, both presence
of more than 3 metabolic risk factors and the presence of
high waist circumference are associated risk of type 2
diabetes.

5. Case studies…
 In some case series studies, it reported that
prevalence of metabolic syndrome high with patients
with gout. Hyperuricemia has been associated with
metabolic syndrome in studies of both healthy
individuals and patients may also precipitate
cardiovascular diseases of which metabolic syndrome
is a strong risk factor.
 The most difference in the prevalence of
hyperuricemia was found in male adults with
metabolic syndrome, compared with those with none
metabolic syndrome.

6.  Higher prevalence of metabolic syndrome was also found
in men with hyperuricemia. Even in those with normal
uricemia, higher serum uric acid levels were associated
with metabolic syndrome.
 In those with normal BMI, the prevalence of metabolic
syndrome was more than 10 fold higher in those with uric
acid levels of 10 mg/dl or greater compared with uric acid
levels less than 5 mg/dl.
 Thus, all data shows us that, those with hyperuricemia are
always cormorbidited with metabolic syndrome.

7.  Elevated mean serum uric acid levels were found to be
significantly increase by the component numbers of
metabolic syndrome and further more, the prevalence of
metabolic syndrome also increased significantly with uric
acid levels.
 Higher uric acid levels are associated with metabolic
syndrome and the converse is true that patients with
hyperuricemia frequently have metabolic syndrome. It
was therefore suggested that, insulin resistance is the
pathophysiology mechanism for the association

8. Metabolic syndrome with insulin
resistance
 The abnormal components of metabolic syndrome usually
cogent conceptual pathogen to reflect the essential
cause. However, insulin resistane is a common feature of
patients with abnormal metabolic components.
 Insulin secreted by pancreatic beta cells cause the cells to
take up glucose from blood and when the cells have a
reduced sensitivity to stimulation of glucose uptake or
insulin in the face of normal or raised glucose
concentration, the situation is defined as insulin
resistance.

9.  If insulin resistance exits, more insulin needs to be
secreted by the pancreas with resultant compensatory
hyperinsulinemia.
 The result is glucose intolerance and hyperglycemia and
subsequently type-2 diabetes. In addition,
hyperinsulinemia may aggravate insulin resistance by
interfering with insulin signaling pathways and further
excavating insulin resistance

10. Continued…
 Insulin resistance is thought to be an important
correlate of other risk factors of metabolic
syndrome such as dyslipidemia and hypertension.
 Patients with essential hypertension were found
to be associated with insulin resistance and even
among the normotensive population. Insulin
resistance is shown to be associated with high
blood pressure levels.

11.  Insulin has a direct effect in the dilation of peripheral
vasculature.
 Hyperinsulinemia could lead to hypertension by activating
renin-angiotensin system and subsequently to decrease
renal blood flow, increased urate re-absorption and
xanthine oxidase production resulting in hyperuricemia,
As urate concentration increases in physiologic fluids, the
risk for supersaturation and crystal formation generally
increases hence gout.

12. Conclusion of the relationship between
adiposity, insulin resistance and gout.
Adiposity insulin resistance hyperinsulinemia,
 hyperuricemia inhibition of urate excretion
 GOUT
 Adiposity leads to insulin resistance which leads to hyperinsulinemia,
leading to inhibition of excretion urate by the kidney leading to
hyperuricemia, hence gout.