Mini Review - (2023) Volume 14, Issue 7
Patients with diabetes are more likely to get certain cancers. However, little research has been done to determine whether diabetes may raise the risk of thyroid cancer. This paper examines and summarises the current research on the association between thyroid cancer and diabetes mellitus as well as potential underlying mechanisms. Epidemiologic research revealed significant or insignificant increases in the risk of thyroid cancer in diabetic women and no change in the risk of thyroid cancer in diabetic males. The summary hazard ratio (95% confidence range) for women was 1.19 (0.84-1.69) and for men was 0.96 (0.65-1.42), according to a recent pooled analysis that included 5 prospective studies from the USA. As a result, the findings are debatable and the link between diabetes and thyroid cancer is probably tenuous. To prove their connection, more research is required. Elevated levels of thyroid stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D insufficiency, and anti-diabetic drugs like insulin or sulfonylureas are some of the proposed explanations for such a potential relationship between thyroid cancer and diabetes.
Type 2 diabetes mellitus • Thyroid cancer • Insulin • Anti diabetic drugs • Epidemiologic
Diabetes has been significantly more common during the past few decades. Diabetes is linked to an increased risk of several cancers, including non-lymphoma, Hodgkin's pancreatic cancer, breast cancer, bladder cancer, and prostate cancer. In the meantime, thyroid cancer is becoming more common at one of the quickest rates of all malignancies [1]. According to a survey conducted in the United States, the incidence of thyroid cancer grew by 2.4 times between 1973 and 2002, with tumours measuring 2 cm or less accounting for 87% of the rise. However, thyroid cancer mortality remained consistent during this time. The increased ability of thyroid ultrasonography and ultrasound-guided fine needle aspiration cytology to detect early stage cancers is thought to be the main contributor to this rise in prevalence. This, however, is unable to account for the elevated prevalence before the widespread use of ultrasound [2].
Additionally, it is unable to account for the rise in big (>5 cm) papillary thyroid cancer incidence. As a result, there could be some other causes for the rising number of thyroid cancer cases. Epidemiologic research shows that the sole known risk factor is exposure to ionising radiation. Potential thyroid cancer risk factors include benign thyroid disorders and insufficient or excessive iodine intake. None of them are able to explain the rise in thyroid cancer cases [3]. According to statistical study, cancer development may be influenced by diabetes, obesity, and the metabolic syndrome. Whether diabetes increases the risk of thyroid cancer is unclear. In this essay, we examine the research on the linkage between diabetes mellitus and thyroid cancer as well as the theories put up to explain why this association exists.
The National Cancer Institute's (NCI) Surveillance, Epidemiology and End Results (SEER) cancer registry connected to Medicare claims served as the study's data source [4]. At this time, SEER has information on cancer incidence and survival from 17 population based cancer registries across the United States, which account for about 28% of the country's population. Patients meeting all of the following criteria were included: They were diagnosed with breast, colorectal, lung, or prostate cancer, the four most common types in the elderly, between January 1, 1999, and December 31, 2002. Medicare enrolment and claims data, which are available for 93% of those aged 65 years in the SEER registry, are linked to cancer registry data in SEER medicare. They had at least 24 months of medicare part A (hospital) and part B (outpatient) fee for service coverage previous to the diagnosis of cancer, and this was their first and only case of cancer [5]. Patients were disqualified for the following conditions: in situ lung or prostate cancer, in situ prostate cancer, male breast cancer, cancer diagnosed by death certificate or autopsy, death within one month of diagnosis, missing or unknown cancer stage at diagnosis (due to small numbers of patients).
In order to determine the percentage of all diabetes cases undiscovered till cancer, patients with pre existing diabetes who had been diagnosed between 24 and 4 months (inclusive) prior to cancer were first included in the study (i.e., using a denominator of pre-existing plus undiagnosed until cancer) [6]. Patients with diabetes were, however, afterwards omitted from all analyses of risk variables for undetected diabetes because they already had the disease. Diabetes was defined as the presence of one of the following international classification of diseases, 9th revision, clinical modification diagnosis codes in one inpatient Medicare claim or in two outpatient claims that were submitted at least 30 days apart: 250.xx for diabetes and complications, 357.2x for diabetic polyneuropathy, 362.0x for diabetic retinopathy, and 366.41 for diabetic cataract. To lessen the possibility of misclassifying those patients, laboratory claims were removed [7].
Diabetes has a detrimental impact on the prognosis following a cancer diagnosis and considerably raises the risk for a number of cancers. The relative risk brought on by diabetes mellitus is highest (about two times or more) in relation to malignancies of the liver, pancreas, and endometrial and is lowest in relation to cancers of the kidney, bladder, breast, colorectal, oesophagus, biliary system, and lymphoma. While there seems to be a very low risk of stomach and lung cancer, having a history of diabetes mellitus lowers your risk of developing prostate cancer. Short and long term survival rates for cancer patients with diabetes are lower than those for cancer patients without diabetes. It is quite likely that diabetes, which independently contributes to cancer's deleterious effects on thrombosis and oxygenation, immunological response, as well as the cardiovascular risks associated with cancer surgery, may be enhanced.
Numerous putative pathophysiological pathways may contribute to the interdependence of cancer and diabetes because both conditions are heterogeneous, complicated diseases with complex underlying causes.
Diabetes is characterised by low grade chronic inflammation, decreased antioxidant capacity, dyslipidemia, hypertension, procoagulation, adipose tissue expansion with an unfavourable cytokine secretory profile, and altered hormone concentrations in addition to hyperglycemia and insulin resistance. This relationship between diabetes and cancer may be influenced by diverse genetic characteristics among ethnic groups, variations in lifestyles, and environmental exposures, adding layers of complexity to the situation.
As the liver, muscles, and adipose tissue become more insulin resistant, hyperinsulinemia develops as a coping mechanism. When pancreatic cells are unable to produce insulin intensively, overt diabetes develops. Numerous epidemiological studies that reported a connection between high postprandial, fasting, and C-peptide levels and the risk of developing cancer were compiled and meta-analyzed. The highest categories of insulin/peptide C levels were found to significantly enhance the risk of colorectal, pancreatic, breast, and endometrial malignancies. Insulin is a powerful growth factor with a variety of direct and indirect proliferative and carcinogenic effects. By blocking IGFBP1 in the liver, hyperinsulinemia increases the amount of accessible IGF and may also make cells more sensitive to this hormone. Insulin and IGF have been shown to have growth-promoting and apoptosis-inhibiting activities when present in physiological quantities. The migration of tumour cells may potentially be aided by hyperinsulinemia. Additionally, both cancer cells and normal tissue have high levels of expression for the insulin and IGF receptors. More often expressed is the IR-A receptor, which has a stronger mitogenic than metabolic effect. Additionally, insulin resistance results in a failure of the metabolic cell response while maintaining the downstream effects of mutagenesis signalling. Phase III results were poor, despite early phase clinical trials showing that (IGF1R) specific antibodies increase the sensitivity of colon cancer stem cells to chemotherapy.
The possibility of hyperglycemia is another reasonable explanation. Strong epidemiological data shows that increased cancer incidence and mortality are related to higher sugar intake and elevated serum glucose levels [8]. According to animal studies, hyperglycemia has been linked to metastatic processes, and high glucose environments independent of hyperinsulinemia are associated with considerably larger liver tumours. In animal models, increased production of AGE has been shown to promote the growth of melanoma, pancreatic, and probably colon cancer. Since cancer cells heavily rely on glycolysis, hyperglycemia may directly promote the growth of tumours. The additional beneficial effect of hyperglycemia is unclear because malignant cells are already adapted to highly effective glucose uptake independent of insulin signalling, despite the fact that generation of ATP requires by far more glucose than oxidative phosphorylation (feature used in PET imaging).
Although elements of epigenetic signalling have also been identified in the genesis of cancer, which have been linked to inherited or acquired genetic mutations, epigenetic alterations may offer another probable pathway tying the etiologies of cancer and diabetes. Conversely, diabetes exhibits a variety of endocrinological dysregulations, including elevated levels of bioavailable estrogens as a result of decreased liver SHBP production or elevated androgen production in the ovaries [9]. These elements could raise the risk of endometrial and breast cancer. One of the crucial phases in the development of DM is the expansion of adipose tissue, which is now recognised as a highly active gland. The polypeptide hormones known as adipokines, which are produced by adipocytes, control the immune system, angiogenesis, insulin sensitivity, glucose metabolism, and angiogenesis. The two adipokines that are secreted most frequently, leptin and adiponectin, indicate opposing metabolic activities. Although leptin has a positive correlation with diabetes, obesity, and metabolic syndrome, it may also have a mitogenic effect on breast and pancreatic cancer cells due to its proangiogenic and antiapoptotic features. In contrast, adiponectin controls diabetes negatively and has been found to prevent the growth of cancer through putative pro-apoptotic, anti-inflammatory, and antiangiogenic effects.
It appears that the unfavourable secretory profile of adipokines directly contributes to the development of insulin resistance and may also promote the growth of cancer. Last but not least, it's important to understand that DM related carcinogenic risks may harm more people than is typical. A third of diabetics go undetected, and 35% of US individuals have prediabetes, which is characterised by metabolic abnormalities that are already forming and may encourage the development of cancer. According to epidemiologic studies, the risk of cancer is higher for the latter group. Insulin resistance, altered glucose, fat metabolism, chronic hormonal, inflammatory, and persistent oxidative stress all plays a role in the broad spectrum of DM pathogenesis. The accumulations of random genetic mistakes that lead to the metaplasia dysplasia carcinoma sequence are thus more likely to occur as a result of diabetes [10]. These cycles of persistent cellular destruction and subsequent proliferation are characterised by continuous cycles of cellular death.
Cancer has just been added to the list of diseases for which diabetes puts a person at high risk. Clarifying the link between diabetes and cancer is crucial given the rapidly rising incidence of diabetes worldwide. Given the intricate reciprocal interactions of the pathophysiological pathways producing diabetes, there may be a variety of direct and indirect mechanisms that raise the risk of cancer. The burden of both diseases, which already have a significant impact on public health and the economy, should not be shared, so further mechanistic studies are required to identify the biological pathways that connect them. Once this is done, effective clinical preventive strategies and public health policies should be developed.
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Citation: Shi Y. "Brief Note on Diabetes and Cancer Risk". J Diabetes Metab, 2023, 14(5), 1-2.
Received: 17-Dec-2022, Manuscript No. JDM-22-20989; Editor assigned: 20-Dec-2022, Pre QC No. JDM-22-20989 (PQ); Reviewed: 03-Jan-2023, QC No. JDM-22-20989; Revised: 29-Mar-2023, Manuscript No. JDM-22-20989 (R); Published: 06-Apr-2023, DOI: 10.35248/2155-6156.14.4.1000998
Copyright: © 2023 Shi Y. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
