Diabetes and Insulin by Ty Willison on Prezi
Risk factors associated with colorectal cancer can be integrated into a causative model centering on the relationship between VAT, insulin, and colorectal cancer . Through this sequence of events, glucose is then taken into the cell and can be used by the cell for energy. Without this necessary protein, or if insulin resistance . A computational model of insulin secretion and glucose metabolism for assisting .. on the relation between the damping factor α and the natural frequency ω0.
Patients with colorectal cancer did not differ from those without colorectal cancer in terms of smoking, current use of aspirin, alcoholic drinks consumed per week, percent of fat calories in diet, or mean number of vegetable or fruit servings per week Table 1. Median follow-up time was Although mean physical activity levels were lower in case patients Table 1this did not reach statistical significance.
Regardless, physical activity was adjusted for in the subsequent analysis. Associations With Incident Colorectal Cancer The relationships between baseline glucose, insulin, anthropometric measures, lipid levels, and incident colorectal cancer in men and women in Cox proportional hazards models adjusted for age, sex, and physical activity are presented in Table 2.
For each of the covariates, the sex-specific range of values of the quartiles is listed. Glucose and insulin levels 2 hours after oral glucose challenge were also significantly related to colorectal cancer.
For 2-hour glucose levels Q4 versus Q1there was a 2. Quartile analysis of fasting insulin levels suggested a threshold effect, with an adjusted RR of 1. A linear relationship across quartiles was not evident, but risk appeared to rise at Q2. A model comparing participants in Q2 through Q4 with those in Q1 showed that the adjusted RR for a higher level of waist circumference was 1.
Repeating these analyses with adjustment for diabetes or by exclusion of diabetics did not change the RR estimates. Triglyceride and HDL levels were not statistically significantly associated with colorectal cancer Table 2. An exploratory subset analysis of risk by sex was performed. There were 59 colorectal cancers among men and 43 cancers among women.
The results suggested that the relationship between 2-hour insulin and waist circumference and colorectal cancer is largely accounted for by the results in men.
The relationship between those with glucose intolerance or diabetes defined by baseline blood glucose, medication history, and the results of the oral glucose load and incident colorectal cancer are presented in Table 3.
To determine if the results were affected by alterations in covariate levels due to prevalent cancer that had not yet reached clinical attention, we repeated the analysis, excluding 22 patients who had been diagnosed in the 1st year of follow-up.
The point estimates for RR did not change. The mean risk-factor levels by year of diagnosis were also examined.
There was no evidence of a temporal pattern to suggest an effect due to subclinical disease Table 4. D iscussion In this prospective cohort study in elderly U. Increased waist circumference also was associated with an approximately twofold increased risk for colorectal cancer. The level of increased risk observed with these variables is substantial and equals or exceeds that of other recognized risk factors for colorectal cancer, such as having a first-degree relative with colorectal cancer 30 or consuming a high-fat or low-fiber diet 31 - The demonstration of a relationship between waist circumference and metabolic parameters associated with VAT and colorectal cancer supports a link between VAT and colorectal cancer.
Abdominal obesity has been linked to cardiovascular disease 35 - 37diabetes 3839and overall mortality Data suggest that abdominal obesity may also be associated with breast 41colon 4and prostate 42 neoplasia. While epidemiologic studies have shown an association between waist circumference and waist-to-hip ratio and colorectal cancer 4to our knowledge this study is the first to demonstrate an association between measures of insulin exposure and colorectal cancer.
These data directly support in vitro biologic studies that show a growth-promoting effect of insulin on colorectal cancer 9 - Our findings of a relationship between fasting glucose and insulin levels as well as glucose and insulin levels 2 hours after glucose challenge and colorectal cancer are consistent with data linking diabetes to colorectal cancer risk.
While some studies have not shown a statistically significant association between diabetes and colorectal cancer 47 - 49small sample size and an inability to account for important covariates may have limited those investigations. A recent report 50 from a prospective cancer mortality study of more than 1 million U. The inability to show statistical significance may be secondary to a lack of power due to the small number of case subjects and the low level of increased risk. The increased risk of colorectal cancer observed with higher fasting insulin as well as higher insulin levels 2 hours after glucose challenge in this cohort is consistent with the increased risk of colorectal cancer seen with non-insulin-dependent diabetes because most individuals with this type of diabetes tend to be insulin resistant and to have higher levels of circulating insulin The association with 2-hour stimulated glucose and insulin levels in this elderly population is of interest, because post-prandial glucose and insulin levels rise to higher levels and remain elevated for a longer period in the elderly Some studies 5354 have shown a relationship between dietary glucose intake and colorectal cancer, but the biologic basis for this relationship is unknown.
It should be emphasized that our results relating measures of insulin, glucose, and waist circumference to colorectal cancer risk were independent of the presence of diabetes.
Thus, nondiabetics appear to have an elevated risk of colorectal cancer as their fasting insulin and glucose rise, even if glucose levels do not reach levels defined as consistent with diabetes. Hyperinsulinemia is thought to be a consequence of insulin resistance.
Although our results suggest an association between insulin and colorectal cancer, it is not known whether the mechanism that renders individuals insulin resistant also attenuates the insulin effect on colorectal cancer.The Insulin Glucose Connection Model
The hypothesized causative model relating VAT, insulin, and colorectal cancer benefits from integrating a variety of risk factors for colorectal cancer into a coherent scheme. For example, VAT accumulates with increased age 55 - 57and this parallels the increased incidence in colorectal cancer that occurs with aging. Although this study was not adequately powered to investigate the independent associations within each sex, our study is suggestive of a stronger relationship between VAT and colorectal cancer in men than in women.
The link between physical activity and colorectal cancer risk can also be accounted for by invoking a role for VAT. Surprisingly, a strong association between increased LDL levels and decreased risk of colorectal cancer was identified. The explanation for this finding is unclear. There was no relationship between subclinical evidence of atherosclerotic disease, such as carotid artery stenosis, and colorectal cancer data not shownalthough subclinical atherosclerotic disease is associated with increased LDL Excluding colorectal cancer diagnosed in the 1st year of observation did not alter the relationship, nor was there a pattern of low LDL levels in the first few years of follow-up to suggest subclinical prevalent disease as the cause of the observed association Table 4.
Further research on this unexpected finding is required. The link between VAT, as estimated by waist circumference, may be stronger than that observed because waist circumference only approximates VAT. For example, in studies using computerized tomographic measurement as a gold standard assessment of VAT, the VAT value estimated by anthropometric variables, such as sagittal diameter or BMI, varied by as much as a factor of 3 in both men and women Thus, inaccuracies in the estimation of VAT by using waist circumference as a surrogate measure may attenuate the actual association.
Although these data are consistent, we did not demonstrate, as one might expect, an association between triglyceride levels and colorectal cancer because triglyceride levels increase with increased amounts of VAT.
Similarly, although HDL levels, which are inversely related to VAT, were somewhat lower in patients with colorectal cancer, this did not reach statistical significance.
The small number of case patients and the limited follow-up in this cohort may have diminished our ability to demonstrate these associations. IGFs are acknowledged as potentially important mitogens for many types of malignancy 10 The relationship of obesity, and in particular abdominal obesity, to the IGF family of peptides, binding proteins, and receptors is not well established.
A recent nested case-control study 65 found a statistically significant association between IGF-1 and colorectal cancer. However, in both type I and type II cases, the human body loses its ability to regulate blood sugar, which causes a significantly negative effect on the patients' quality of life or even be potentially fatal. It is a common knowledge that blood glucose concentration in normal humans is maintained within a precise and stable range.
Many external and internal factors affect the level of blood glucose such as food intake, rate of digestion, excretion, exercise, sleep, and psychological state.
These individual or combinational influences constantly alter the physiological processes that regulate plasma glucose level. For instance, if blood glucose is elevated, after a regular meal i. The secreted insulin, then, leads to the uptake of glucose from the blood into the liver and other cells, such as muscle cells. Thus, blood glucose level will eventually go down to the normal range.
Human Insulin molecule scientific 3D model
On the other hand, blood glucose level may decrease imminently due to muscular activity, particularly when food intake is confined. These cells then release glucagon that act on the cells of the liver to initiate the release of glucose.
This results in blood glucose level elevating back to the normal range. Briefly, these islet-cell arguments establish the fact that the capacity to lower blood glucose depends on the responsiveness of the pancreatic beta-cells to glucose and the sensitivity of the glucose utilized by tissues to the released insulin. Furthermore, a shortage of plasma insulin and low glucose tolerance, resulting in a serious inability to lower blood glucose, will cause insulin resistance, which is the key symptom underlying the potential development of diabetes.
However, to tackle diabetes disease and obesity problems, clinicians and researchers are now turning to mechanism-based mathematical models to reach quantitative diagnoses of glucose intolerance and insulin resistance, and also to predict the likely outcomes of therapeutic interventions.
Their ultimate goal is to develop a mathematical model that can be used to accurately predict the outcomes and most successful treatment options for people who have diabetes. The fundamental nature of a good mathematical model must be simple in design and exhibit the basic properties of the real system that we are attempting to simulate and understand.
All well-developed models should be validated and tested against empirical data. In a practical sense, the quantitative comparisons of the model to the real system should lead to an improved mathematical model. The successful model can be applied to suggest the corresponding experiment to highlight a particular aspect of the weakness or problem, which may improve the method of data collection or the procedure of experimental processes.
Thus, modeling itself is an evolutionary process, which is a evolving procedure in which something changes into a different but better form.
Similarly, developing and using a successful mathematical model will guide us to learn more about certain simulating or existing processes rather than finding an entirely actual state of the system. Several reviews have been devoted to mathematical models and diabetic disease  —  and are worthwhile to be referenced. Other than those reviewing journal articles, a pioneering work on modeling the glucose-insulin regulatory system and its ultradian insulin secretory oscillations can be traced back to Bolie .
In this pioneering study, a system of glucose-insulin regulation in terms of coupled differential equations of feedback was analyzed with the so-called critical damping criteria of a self-regulating feedback system i.
The secretion of insulin in the glucose-insulin endocrine metabolic system occurs in an oscillatory manner over a range of min and is usually referred to as ultradian oscillations .
In andAckerman et al. In the following sections, we will introduce their conceptually illuminating model in greater detail, and also develop our computational model, which will be validated by using their model equations and other published experimental data and results. In order to determine whether or not a patient has pre-diabetes or diabetes, health care providers usually conduct a fasting plasma glucose FPG test or a GTT.