Please Scroll Down to See Forums Below 
Tatyana
Elite Mentor
I get a number of alerts for new journal articles sent to me. I got this one yesterday.
Study protocol: Insulin and its role in cancer
BMC Endocrine Disorders 2007,
7:10 doi:10.1186/1472-6823-7-10
K Harish ([email protected])
M Dharmalingam ([email protected])
M Himanshu ([email protected])
ISSN 1472-6823
Article type Study protocol
Submission date 16 July 2007
Acceptance date 22 October 2007
Publication date 22 October 2007
Article URL http://www.biomedcentral.com/1472-
Abstract
Background: Studies have shown that metabolic syndrome and its consequent
biochemical derangements in the various phases of diabetes may contribute to
carcinogenesis. A part of this carcinogenic effect could be attributed to
hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding
proteins and hence increase levels of free IGF-1.
It is well established that bioactivity
of free insulin growth factor 1 (IGF-1) increases tumor turnover rate.
The objective is
to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying
the relation between insulin resistance/sensitivity and IGF-1 levels in cancer
patients. We postulate that hyperinsulinaemia which prevails during initial phases of
insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-
1, which may contribute to process of carcinogenesis.
Methods / Design: Based on our pilot study results and power analysis of the same,
we have designed a two group case-control study. 800 proven untreated cancer
patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200
healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1
levels shall be determined in all subjects. Association between the two parameters
shall be tested using suitable statistical methods.
Discussion: Well controlled studies in humans are essential to study the link
between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study
could provide insights to the role of insulin, insulin resistance, IGF-1 in
carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve
around insulin and insulin resistance.
Background
The association of diabetes mellitus and cancer has been reported more than 100
years ago [1]. Population studies have shown increased evidence of this
association.
Diabetes has been recognized as a risk factor for development of
breast, endometrial, colorectal and pancreatic carcinomas [2]. Breast, endometrial,
colorectal and pancreatic carcinomas are best studied with regard to their
association with diabetes/insulin resistance. Population studies have shown that the
effects of diabetes mellitus on colorectal cancer may be mediated through
mechanisms ranging from increased colonic transit time to hyperinsulinaemia. In
relation to the latter, at least in the early phase of development, type 2 diabetes
mellitus is associated with increased circulating insulin concentrations [3, 4]. A large
cohort study concluded that diabetes is associated with a modestly increased risk for
endometrial cancer among women [5]. Future research, particularly prospective
studies with biological samples, could be very helpful in answering questions aimed
at clarifying these mechanisms [5]. Data suggest that type 2 diabetes might be
associated with up to 10–20% excess risk for breast cancer and that it could also
have detrimental effects on the natural history, diagnosis, and treatment of breast
cancer [1, 6].
In the past few years both laboratory investigations and population studies have
provided some circumstantial evidence that insulin growth factor biochemical derangements may contribute to carcinogenesis.
Several studies
implicate hyperinsulinism, a condition that prevails prior to the onset of diabetes (part
of metabolic syndrome) as candidate mediator in carcinogenesis [10].
Studies have
revealed that high levels of circulating insulin decreases levels of insulin like growth
factor binding protein 1 and 3 (IGFBP 1,3). Thus free IGF-1 levels increase in
circulation [11, 12].
Another aspect of IGF physiology is the IGF signaling. In this
signaling process, IGF-1 receptor is a predominant factor and is crucial for tumor
transformation and survival of malignant cell. It has comparatively less role in normal
cell growth [13].
Thus role of IGF-1 in promoting carcinogenesis and its prognosis is
well established. Over the recent years, IGF-1 physiology has been widely studied.
The IGF system, comprises of insulin-like IGF-I, IGF-II, and IGFBPs. IGF-1 as a
growth factor plays a dominant role over IGF-2 and hence is widely studied.
Until
recently, growth hormone was the only known stimulant of IGF-1 production.
Different lines of evidence suggest that the IGF/IGFBP system may be regulated by
factors other than growth hormones. States of nutritional deprivation, such as
starvation and protein caloric under-nutrition and type 1 diabetes mellitus, in animal
models have long been known to influence the production of IGFs [14-16]. Various
studies have shown that resistance to insulin action, as found in diabetic patients,
has been associated with an increase IGFBP-3 protease activity, there by reducing
IGFBP-3 levels [17]. Also, Insulin increases IGF-I bioavailability through IGFBP-1
suppression [14, 18, 19]. Thus there is ample evidence to suggest that insulin
resistant states increase free IGF-1 levels.
Medical literature suggests that well controlled biochemical and genetic studies are
required to establish the link between insulin, IGF-1, diabetes and cancer. We
propose to investigate the role of hyperinsulinemia in carcinogenesis.
The primary objective of the study is to investigate the role of insulin resistance or
sensitivity in carcinogenesis.
This is done by studying the relation between insulin
resistance/sensitivity and IGF-1 levels in cancer patients. The secondary objective is
to study the above mentioned association with organ specific cancers if possible.
Carcinogenesis is multi-factorial.
The metabolic and genetic derangements that take
place during carcinogenesis may be induced by carcinogens and inherited genetic
factors. The role of either could be variable in a given case. We hypothesize that
people with insulin resistance are at risk of developing cancer due to high levels of
circulating IGF-1. Such a risk would increase if other such factors are prevalent /
acquired. A person with high levels of IGF-1 may be predisposed to cancer and
his/her risk of developing cancer would increase with the presence of other such
factors. Cancer being a non-communicable disease, with multiple risk factors,
modifiable risk factors are very few.
Controlling hyperinsulinaemia would modify one
major risk factor. IGF-1 levels in body change with age. In addition, riskIGF-1 has high bioactivity on epithelial cells. Thus their role in carcinomas is of
significance rather than other types of malignancies. Hence we limit our study to
carcinomas of breast, GIT, liver, prostate, uterus, cervix and ovaries.
Study protocol: Insulin and its role in cancer
BMC Endocrine Disorders 2007,
7:10 doi:10.1186/1472-6823-7-10
K Harish ([email protected])
M Dharmalingam ([email protected])
M Himanshu ([email protected])
ISSN 1472-6823
Article type Study protocol
Submission date 16 July 2007
Acceptance date 22 October 2007
Publication date 22 October 2007
Article URL http://www.biomedcentral.com/1472-
Abstract
Background: Studies have shown that metabolic syndrome and its consequent
biochemical derangements in the various phases of diabetes may contribute to
carcinogenesis. A part of this carcinogenic effect could be attributed to
hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding
proteins and hence increase levels of free IGF-1.
It is well established that bioactivity
of free insulin growth factor 1 (IGF-1) increases tumor turnover rate.
The objective is
to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying
the relation between insulin resistance/sensitivity and IGF-1 levels in cancer
patients. We postulate that hyperinsulinaemia which prevails during initial phases of
insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-
1, which may contribute to process of carcinogenesis.
Methods / Design: Based on our pilot study results and power analysis of the same,
we have designed a two group case-control study. 800 proven untreated cancer
patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200
healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1
levels shall be determined in all subjects. Association between the two parameters
shall be tested using suitable statistical methods.
Discussion: Well controlled studies in humans are essential to study the link
between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study
could provide insights to the role of insulin, insulin resistance, IGF-1 in
carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve
around insulin and insulin resistance.
Background
The association of diabetes mellitus and cancer has been reported more than 100
years ago [1]. Population studies have shown increased evidence of this
association.
Diabetes has been recognized as a risk factor for development of
breast, endometrial, colorectal and pancreatic carcinomas [2]. Breast, endometrial,
colorectal and pancreatic carcinomas are best studied with regard to their
association with diabetes/insulin resistance. Population studies have shown that the
effects of diabetes mellitus on colorectal cancer may be mediated through
mechanisms ranging from increased colonic transit time to hyperinsulinaemia. In
relation to the latter, at least in the early phase of development, type 2 diabetes
mellitus is associated with increased circulating insulin concentrations [3, 4]. A large
cohort study concluded that diabetes is associated with a modestly increased risk for
endometrial cancer among women [5]. Future research, particularly prospective
studies with biological samples, could be very helpful in answering questions aimed
at clarifying these mechanisms [5]. Data suggest that type 2 diabetes might be
associated with up to 10–20% excess risk for breast cancer and that it could also
have detrimental effects on the natural history, diagnosis, and treatment of breast
cancer [1, 6].
In the past few years both laboratory investigations and population studies have
provided some circumstantial evidence that insulin growth factor biochemical derangements may contribute to carcinogenesis.
Several studies
implicate hyperinsulinism, a condition that prevails prior to the onset of diabetes (part
of metabolic syndrome) as candidate mediator in carcinogenesis [10].
Studies have
revealed that high levels of circulating insulin decreases levels of insulin like growth
factor binding protein 1 and 3 (IGFBP 1,3). Thus free IGF-1 levels increase in
circulation [11, 12].
Another aspect of IGF physiology is the IGF signaling. In this
signaling process, IGF-1 receptor is a predominant factor and is crucial for tumor
transformation and survival of malignant cell. It has comparatively less role in normal
cell growth [13].
Thus role of IGF-1 in promoting carcinogenesis and its prognosis is
well established. Over the recent years, IGF-1 physiology has been widely studied.
The IGF system, comprises of insulin-like IGF-I, IGF-II, and IGFBPs. IGF-1 as a
growth factor plays a dominant role over IGF-2 and hence is widely studied.
Until
recently, growth hormone was the only known stimulant of IGF-1 production.
Different lines of evidence suggest that the IGF/IGFBP system may be regulated by
factors other than growth hormones. States of nutritional deprivation, such as
starvation and protein caloric under-nutrition and type 1 diabetes mellitus, in animal
models have long been known to influence the production of IGFs [14-16]. Various
studies have shown that resistance to insulin action, as found in diabetic patients,
has been associated with an increase IGFBP-3 protease activity, there by reducing
IGFBP-3 levels [17]. Also, Insulin increases IGF-I bioavailability through IGFBP-1
suppression [14, 18, 19]. Thus there is ample evidence to suggest that insulin
resistant states increase free IGF-1 levels.
Medical literature suggests that well controlled biochemical and genetic studies are
required to establish the link between insulin, IGF-1, diabetes and cancer. We
propose to investigate the role of hyperinsulinemia in carcinogenesis.
The primary objective of the study is to investigate the role of insulin resistance or
sensitivity in carcinogenesis.
This is done by studying the relation between insulin
resistance/sensitivity and IGF-1 levels in cancer patients. The secondary objective is
to study the above mentioned association with organ specific cancers if possible.
Carcinogenesis is multi-factorial.
The metabolic and genetic derangements that take
place during carcinogenesis may be induced by carcinogens and inherited genetic
factors. The role of either could be variable in a given case. We hypothesize that
people with insulin resistance are at risk of developing cancer due to high levels of
circulating IGF-1. Such a risk would increase if other such factors are prevalent /
acquired. A person with high levels of IGF-1 may be predisposed to cancer and
his/her risk of developing cancer would increase with the presence of other such
factors. Cancer being a non-communicable disease, with multiple risk factors,
modifiable risk factors are very few.
Controlling hyperinsulinaemia would modify one
major risk factor. IGF-1 levels in body change with age. In addition, riskIGF-1 has high bioactivity on epithelial cells. Thus their role in carcinomas is of
significance rather than other types of malignancies. Hence we limit our study to
carcinomas of breast, GIT, liver, prostate, uterus, cervix and ovaries.
