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The coexistence of diabetes & cancer continues to be of interest and raises question as
to possible relationship. Is cancer more common in persons with diabetes than those without it and vice versa? Many studies have been carried out over the years and there is no unanimity of opinion. Fundamentally, the question is;- Is there simply a chance association or is there a significant correlation between cancer and diabetes?
Wilson & Maher observed that diabetes and cancer occurred together much more
frequently than would be expected if it were assumed that the two diseases were independent.1 Ellinger & Landsman found that among 1280 diabetic patients seen at Montefiore Hospital in N.Y city from 1933 to 1941, 3.04% had malignant disease. This incidence of cancer was six and one half times greater than that for cancer in general population (0.46%) of state of New York in 1941).
Jacobson, using data from death certificates & matched Hospital case histories to obtain a
selected sample of causes of death among white persons in N.Y. city concluded that cancer is more common among diabetics than non diabetics.' In a study of 6317 autopsy records herdan of the University of Bristol found that malignant tumours occurred in only 10.1% of diabetics, whereas the incidence in non- diabetics was 19.5%. In the series of Warren, lecompte & Legg, comprising 1854 diabetic patients on whom postmortem examination was performed, 224 patients or 12.1% were found to have malignant diseases.
It will be noted that with the advent of insulin in 1922, there was a sharp rise in the
percentage of deaths from, cancer compared with the total number of deaths, reflecting the increasing longevity of diabetic individuals.
Warren, Lecompte & Legg, found that among 214 diabetic women who died of cancer and
were examined at autospy, 23 (10.7%) had cancer of endometrium in contrast to a frequency of about 5% in non diabetic females who died of cancer.
Cancer cachexia
Cancer cachexia is a chronic wasting illness directly associated with the presence of
uncontrolled malignancy. It is aptly viewed as a symptom complex characterised by weight loss, anorexia and asthenia leading to inanition and malnutrition and ultimately death of the patient.
Of the factors associated with cancer cachexia, weight loss is usually the most obvious,
with wasting of body fat and lean body mass presumably due to an imbalance between energy intake and energy expenditure. Whether the weight loss of malignancy results from a reduced caloric intake, increased energy expenditure or a combination of both is unclear. It is appropriate that the incidence and severity of weight loss bears no precise relation to size, site, stage, or histology of tumour.
Although depletion of host tissues in cancer cachexia could result from one of several
mechanisms, inadequate nutrient intake is considered by most to be the dominant factor. Impaired absorption, increased nutrient loss and increased demand for energy, in support of metabolic requirement are potential contributing causes of weight loss. More commonly inadequate food intake results from anorexia which herein is simply defined as a loss of appetite.
Data regarding the incidence of cancer among Joslin Clinic patients are as shown
| Period |
Diabetes Deaths |
Cancer Deaths |
% of cancer deaths of all deaths |
| 1898-1914 |
326 |
5 |
1.5 |
| 1915-1922 |
836 |
32 |
3.8 |
| 1923-1936 |
4157 |
362 |
8.7 |
| 1937-1943 |
3639 |
327 |
9.0 |
| 1944-1955 |
9794 |
972 |
9.9 |
| 1956-1965 |
8302 |
889 |
10.7 |
| 1966-1968 |
912 |
117 |
12.8 |
Most often, it is causally associated with presence of malignancy of mechanisms that are
currently undefined.
An increasing body of evidence supports the concept that factors other than caloric
deprivation alone underlie the weight loss and associated with adverse prognosis in the malnourished cancer patients.
In a series of 254 patients with advanced cancer given a standardized nutritional
assessment, Grosvenor & Colleagues observed essentially no difference in caloric intake in 170 weight losing patients when compared with 63 weight stable patients. As a result, increasing attention has been directed at the role of factors other than reduced caloric intake contributing to the development of weight loss in the cancer population i.e. cancer cachexia due to impaired carbohydrate metabolism.
One of the earliest metabolic abnormalities described in cancer population was glucose
intolerance.
In 1885 Freund reported hyperglycemia in 62 of 70 patients with cancer. Mark & Bishop
found that the rate of disappearance of glucose given intravenously was significantly slower in individuals with cancer than control subjects. Their patients were well nourished and non cachectic. Edmonson noted impaired glucose tolerance and increased free fatty acid utilization in. 20 cachectic patients, with advanced cancer as compared to findings in 17 normal control subjects. Lisker Brody & Beizer reported that the results of oral glucose tolerance tests were abnormal in 52% of 66 patients with malignant blood dyscrasias. In matched controls the frequency of abnormal results was 8.5%. Clicksman, Rawson, Glicksman Meyers & Rawson performed oral G.T.T. upon 950 patients admitted consecutively to the memorial centre for Cancer & allied disease in New York city. Findings rated as abnormal were obtained in 36.7% of 628 patients in whom the diagnosis of cancer was made by tissue examination, as contrasted with abnormal findings in only 2.3% of the control group of 322 patients with lesion proven to be benign. They noted a high frequency of diabetic response in cancer of the endometrium 64% of 25 patients.
Skin Cancer, 47% of 32 patients.
Cancer of soft tissues. 44.4% of 18 patients. Cancer of floor of mouth 45.5% of 32
patients. Lymphosarcoma 54.5% of 11 patients.
Hodgkin's disease 50% of 16 patients. Cancer of thyroid gland 70% of 10 patients.
Four out of five patients with cancer of pancreas had abnormal
results of G.T.T.10-11
The glucose intolerance seen in cancer population is associated with marked resistance
to administered insulin. But the exact mechanism underlying this insulin resistance has not been well defined.
Another abnormality in glucose metabolism consistently seen in cancer patients with
advanced disease is an increase in glucose turnover measured with isotope tracer techniques.
Impact of Antitumour Therapy on Nutrition and Beta Cell Function
Chemotherapy : Therapeutic approaches with cancer chemotherapeutic agents may
profoundly affect the nutritional status of the host. These effects may be direct, by altering intracellular protein or DNA synthesis of host cells, or indirect by producing nausea, vomiting, anorexia and food aversion.
These symptoms result in decreased oral intake, fluid and electrolyte imbalance, general
weakness and weight loss.
Constipation and a dynamic ileus, alternating with diarrhoea are frequently observed and
troublesome complications associated with administration of Vincristine.
Radiotherapy: Radiation therapy can have significant impact on the nutritional status of the host by its effect on the rapidly dividing mucosal crypt cells of the G.I-T. Radiation effects may appear early or late. The early effects are transient and symptoms subside within a few weeks after completion of treatment.
Early symptoms are manifested by diarrhoea with or without gastrointestinal bleeding,
nausea, vomiting, weight loss, mucositis, xerostomia, alteration in taste and food aversion.
Late gastrointestinal complications include stricture fistula, bowel perforation and
malabsorption.
The most common complication observed in patients receiving radiation therapy for pelvic
cancer is radiation induced enteritis.
Combination of chemotherapy and radiotherapy are believed to have a cumulative
adverse effects on the cells of G.I.T. and may damage pancreatic beta cells.
In conclusion, diabetics have greater incidence of cancer of gall bladder, endometrium
and pancreatic carcinoma. If all cancer patients are screened for diabetes there is a definitely greater incidence of abnormal glucose tolerance. This is related to cancer cachexia, malnutrition, effect of chemotherapy and radiotherapy or some unknown mechanism.
REFERENCES
1. Wilson EB & Malher HC: Cancer & Tuberculosis with some comment on cancer and
other disease American J. of cancer 16, 227, 1932.
2. Ellinger F& Landsman H. Frequency & course of cancer in diabetics New York Journal
of Med.44. 259, 1944.
3. Jacobson PH-A statistical study of cancer among diabetics. Millibank Mem. Fund
Quart.26, 90, 1948.
4. Herden G: The frequency of cancer diabetes mellitus British J.of Cancer 14, 449,
1960.
5. Warren S, Lecompte, P.M.& Legg MA. - The pathology of diabetes mellitus 4th
ed.philadlephia & Febiger 1966.Ch.24.
6. Freund E: Zur Diagnose des Carcinoma Wien Med.BL. 8, 268, 1885.
7. Marks, P.A. & Bishop J:- Alteration in carbohydrate metabolism associated with
neoplasia in man Proc. Amer. Asso. Cancer Res, 2, 131,1956 (Abstract).
8. Edmonson JH: - Fatty acid mobilisation & Glucose metabolism in patients with cancer
19, 277, 1966.
9. Lisker, S.A. Brody J.I and Beizer LH:- Abnormal carbohydrate metabolism in patients
with malignant blood dyscrasias. Amer. J. Med. Science 252, 282, 1966.
10. Glicksman A.S & Rawson R.W.:- Diabetes & altered carbohydrate metabolism in
patients with cancer. Cancer 9, 1127, 1956.
11. Glicksman A.S. Myers WPL & Rawson R.W.- Diabetes mellitus and carbohydrate
metabolism in patients with cancer Medical Clinics of North America. 40, 887, 1956.
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