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SUMMARY INSULINE RESISTANCE WAS INCREACED RISK
FACTOR FOR PROSTAT HYPERPLASIA VIA INSULIN LIKE GROWTH FACTOR-1 IN ABDOMINAL OBESITY
Pandemic of obesity, especially abdominal obesity Ab-Ob, recently become serious threat to human being in the world. Ab-
Ob is often acquired with other symptoms and risk factors that considered as cardiovascular disease CVD risk factors which is
known as metabolic syndrome MS Carr
et al.,
2004; IDF, 2013. MS was a risk factors constellation consist of insulin resistance,
Ab-Ob, hypertension, glucose tolerance impairment prediabetes, and dyslipidemia that considered as an initial phase on the natural
history of diabetes mellitus DM and CVD Leahy, 2005; Grundy
et al.,
2008; Gorbanchyski
et al.,
2010. On the natural history of MS as a risk factor of metabolic disorder and CVD, Ab-Ob
occupied the very basic role Carr
et al.,
2004; Grundy
et al.,
2008. Since 1980, obesity pandemic became a fact that have serious
attention from WHO. On 2008, the newest data from WHO showed that more than 1,4 billion world population have an
overweight condition, 200 million male and 300 million female with obesity WHO, 2014. More than 10 world population was
in obesity condition. In United State, 30 adult population was in overweight condition BMI 25-29,9 kgm
2
and 32 with obesity BMI
30 kgm
2
Ogden
et al.,
2006. On the age more than 60 years old, the prevalence even reached 40. In Asia, prevalence of
MS was obtained highest in India due to high prevalence of Ab- Ob, reaching 1.091 population with 8 prevalence on male and
18 on female Johnson, 2013.
Prevalence of DM is also keep increasing from year to year along with increase prevalence of MS and obesity, especially Ab-
Ob. In 2012, International Diabetes Federation IDF was approximating 371 million world people 8,3 suffer from DM
42 IDF, 2012. From that number, half was becoming undiagnosed
cases. Indonesia occupied the 7
th
rank of 10 countries with the largest number of DM in the world IDF, 2012. The number of
DM patient was estimated 7,3 million population on 2011 IDF, 2011. On 2012, the number of DM patient increased to 7,6 million
IDF, 2012. This number is predicted increasing continuously until reach 11,8 million population on 2030. At that time,
Indonesia is predicted on the 9
th
rank countries with the largest number of DM patient in the world. The result of RISKESDAS
from Health Minister on 2007 show prevalence of DM in Indonesia reaching 5,7 Depkes, 2007.
Complication of MS and DM is started early before diagnosis enforced. About 50 patient on the time of diagnosis is already
having chronic complication, 21 among them have retinopathy, 18 with abnormal ECG, and 14 with leg blood flow
disturbance, and the rest is associated with gastrointestinal malignancy and urologic malignancy, especially male IDF 2012;
WHO 2014. That DM complication reduce the patient productivity and life expectancy until 15 years. Four point eight
million people in the world died because of DM due to MS on 2012. Mortality rate of diabetes in Indonesia is quite high, about
155.465 Indonesian population died because of DM IDF, 2012.
Beside as a risk factor constellation that cause DM and CVD, MS or each components, especially Ab-Ob and insulin resistance,
from some epidemiological study, is correlated with some degenerative disease, such as prostate hyperplasia Gorbanchyski
et al.,
2010; WHO, 2014. On male, prostate hyperplasia is one of three most obtained degenerative disease along with increase of
age other than hypogonad and erection dysfunction that related to low grade chronic inflammation. Fifteen percent male population
aged 40 years old were found with prostate disorder and prostatitis, 20-40 with Benign Prostate Hyperplasia BPH. On 2007, there
were 218.890 new cases of BPH in United State with mortality rate reaching 27.050 and the incidence increase continuously reaching
230.000 new cases on 2010 Braun
et al.,
2011.
43 Insulin resistance is defined as resistance to insulin metabolic
effect that will cause tissue insensitivity to insulin Hawkins Rossetti, 2005. Insulin metabolic effect include inhibition of
endogen glucose production, stimulation effect on glucose uptake and tissue glycogen synthesis, and inhibit fat dispersion on adipose
tissue Ghani, 2006. Without any defect on beta cell pancreas function, individu will compensate insulin resistance with
increased number of insulin secretion hyperinsulinemia Masharani
et al.,
2004. Ab-Ob is related to insulin resistance as the cause of
hyperinsulinemia Carr Brunzell, 2004. Ab-Ob is also related to low grade chronic systemic inflammation due to increase
proinflammation cytokin such as CRP and protrombotik state along with increased level of plasminogen activator inhibitor-1
PAI-1 and oxidative stress Kahn
et al.,
2005. Pathogenesis model of this insulin resistance is integrated
between genetic, obesity, and environmental factor Masharani
et al.,
2004; Hawkins Rossetti, 2005; Kahn
et al.,
2005. Genetic mutation affect the insulin action and insulin secretion defect.
Insulin resistance on obesity is related to sirculation factors that result from adipocyte such as TNF-
α Tumor Necrotizing Faktor alfa, FFA Free Fatty Acid, and leptin. However, the most
dominat is FFA Evans
et al.,
2002. Intraabdominal adipose tissue on abdominal obesity will release excess FFA that can induce
insulin resistance because it will compate with glucose as an energy source to be oxidized in periferal tissue. In molecular, FFA
can activate protein kinase C PKC, nuclear factor kappa Beta NF-
қB, mitogen activated protein kinase p38MAPK, NH2- termial jun kinaseStress activated protein kinase JNKSAPK,
that increase serinethreonine phosphorylation on IR or the substrate as a cause of decrease receptor sensitivity to insulin so
that become compensated with hyperinsulinemia condition. This signaling pathways is also have a rule in increasing production of
reactive oxygen species ROS which is in the end will placed MS patient, which already have DM, into oxidative stress and
44 proinflammation condition, especially low grade chronic
inflammation Evans
et al.,
2002; Opie, 2007; Grundy, 2008. Low grade chronic inflammation on MS is happen due to
increase macrophage infiltration to adipose tissue which is marked with increase proinflammation cytokine such as TNF-
, IL-6, and CRP, have a role in insulin resistance pathogenesis and also
considered have a role in prostate hyperplasia incidence Hsing
et al.,
2007. Inflammation on MS which is related to increase prostate hyperplasia incidence is hypothezised through: 1
increase proinflammatory mediator such as cytokin and ROS; 2 increase oncogen ekspression such as COX-2 and MMP; 3
increase proinflammation gene transcription factor such as NF-kB, STAT3 dan HIF-
Bruton
et al.,
2010; Ramos, 2013. If chronic inflammation process, ROS, process series that have been
mentioned above about prostate as target organ can cause focal atrophy of prostate tissue which is accompanied by epitel tissue
proliferation and inflammatory cells infiltration named as PIA prolifereative inflammatory atrophy. PIA will transform become
high grade prostate hyperplasia
PIN Lehrer 2005; Patel
et al.,
2013. Tissue damage and chronic healing process series as repeated compensation of healing cell damage also will accelerate
BPH nodul occurance Briganti
et al.,
2009; Nunzio
et al.,
2011. Secondary hyperinsulinemia condition consequence of insulin
resistence in MS also related prostate hypertrophy and clinical manifestation of Lower urinary tract symptoms LUTS.
Hyperinsulinemia related to increase of sympathetic nerve activity and will increase prostate sympathetic tone so that can worsened
LUTS
symptom that
related to
prostate hyperplasia.
Hyperglycaemia alone will increase cytosolic-free calcium in smooth muscle cells and neuronal tissue will increase sympathetic
nerve activation.
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