The Centenary Celebrations-Insulin and Diabetes.

Most people will know the word diabetes. Few people will not know it has something to do with sugar. Diabetes mellitus is the complete name for the condition, mellitus meaning sweet or honey taste found in the urine. Not to be confused with Diabetes insipidus, a condition of the pituitary gland, the kidney or the Psyche where water cannot be retained by the body and very severe thirst and huge polyuria (passing a huge amount of urine occurs). The condition Diabetes mellitus was known in Egyptian times and in recent times has become so much more prevalent. Alas most people will have a relation with the condition and will be aware that complications can occur such as blindness. Even today with all our new medications and all our new knowledge, still diabetes shortens life span by 10 or so years but this figure is rapidly getting less due to earlier diagnosis and better treatment for high blood sugar, cholesterol and high blood pressure. To go back more than 100 years obese patients who developed diabetes could cure the symptoms which include thirst, passing a lot of urine, tiredness and genital itch by weight reduction and exercise. The reason for this improvement is now known in much more detail than it was then. The hormone insulin which is secreted by the islet cells in the pancreas lowers blood sugar. A deficiency of insulin leads to a rising blood sugar and the high blood sugars are the cause of the thirst. The high blood sugar is no longer able to be contained by the kidney and is secreted in the urine. The high concentration of sugar in the urine pulls out sugar by osmosis, drags with it, water, so the higher the glucose in the blood and urine the more water is pulled through the kidneys which are filters. The increased amount of water thus lost, results in frequency of passing water which is now full of glucose. The loss of water is recognised by the thirst mechanism which gets switched on and being very thirsty the patient with diabetes starts to drink and drink to make up for the loss of water in the urine. Sometimes the patient who might have been keen on lemonade or other sweet drinks just drinks more and more not realising that the drinks are heavily laden with sugar. This results in increasing the blood sugar even higher and even more thirst until the whole system collapses. The patient becomes unconscious very dehydrated and will die unless given intravenous fluids and then insulin. One such lady was a patient of mine. The African lady was so complicated that after she recovered we wrote up her case in one of the medical journals to inform others of the problems we faced and the treatments we gave which resulted in her recovery. Hyperosmolar coma is the name of the condition and thankfully rare. I can of course remember other patients who we were not successful in saving but they are too painful to relate.

Thirst as an ingestive behavior: A brief review on physiology and assessment

Background: Thirst is a sensation normally aroused by a lack of water and associated with a desire to drink more fluid. Aim: The aims of this brief review are twofold: (a) to summarize the thirst mechanism in how it is initiated and diminished, and (b) to describe techniques to assess human thirst accurately in a variety of situations. Discussion: Thirst is maintained via a feedback-controlled mechanism, regulated by central and peripheral factors, as well as social and psychological cues. Most studies of thirst have focused on the initiation of water intake and the neural mechanisms responsible for this vital behavior. Less attention has been paid to the stimuli and mechanisms that terminate a bout of drinking and limit fluid ingestion, such as oropharyngeal and gastric signals, coupled with osmotic sensations. Thirst perception is typically assessed by subjective ratings using a variety of questionnaires, rankings, or visual analog scales. However, the appropriate perceptual tool may not always be used for the correct assessment of thirst perception. Conclusions: In considering the many factors involved in thirst arousal and inhibition, similar questions need to be considered for the correct assessment of this ingestive behavior.

Side-effects of lithium at lower therapeutic levels: the significance of thirst

SynopsisThe prevalence of thirst, subjective polyuria and related side-effects was investigated in 87 patients attending a lithium clinic and in a group of 52 controls. Thirst was surprisingly common, occurring in 67% of patients, in spite of the fact that they had been maintained on relatively low levels of lithium, and was due principally to the lithium rather than to other psychotropic drugs. Urine flow and impaired renal water absorption correlated with the serum lithium level and the length of treatment in the patients, despite the fact that few were clinically polyuric. The pattern of the results confirms previous suggestions that lithium may stimulate the thirst mechanism directly as well as via an increased renal resistance to vasopressin. The possible implications in terms of clinical response are discussed.

Voluntary dehydration and alliesthesia for water

The purpose of this experiment was to explore the complex relationship between fluid consumption and consumption factors (thirst, voluntary dehydration, water alliesthesia, palatability, work-rest cycle) during a simulated 14.5-km desert walk (treadmill, 1.34 m X s-1, 5% grade, 40 degrees C dry bulb/26 degrees C wet bulb, and wind speed of approximately 1.2 m X s-1). Twenty-nine subjects were tested (30 min X h-1, 6 h) on each of two nonconsecutive days. The subjects were randomly assigned to one of three groups: tap water (n = 8), iodine-treated tap water (n = 11), or iodine-treated flavored tap water (n = 10). The temperature of the water was 40 degrees C during one trial and 15 degrees C on the other. Mean sweat losses (6 h) varied between 1.4 kg (warm iodine-treated; 232 +/- 44 g X h-1) and 3.0 kg (cool iodine-treated flavored; 509 +/- 50 g X h-1). Warm drinks were consumed at a lower rate than cool drinks (negative and positive alliesthesia). This decreased consumption resulted in the highest percent body weight losses (2.8 and 3.2%). Cooling and flavoring effects on consumption were additive and increased the rate of intake by 120%. The apparent paradox between reduced consumption concomitant with severe dehydration and hyperthermia is attributed to negative alliesthesia for warm water rather than an apparent inadequacy of the thirst mechanism. The reluctance to drink warm iodine-treated water resulted in significant hyperthermia, dehydration, hypovolemia, and, in two cases, heat illness.

Comparison of body fluid compartment sizes in Brattleboro homozygous and Long-Evans rats

Because of their hypothalamic diabetes insipidus (DI), Brattleboro homozygous rats exhibit profound polyuria and polydipsia with elevated plasma osmolalities. This combination of symptoms has led to the tacit assumption that these animals are chronically volume contracted. However, the few direct measurements that have been published indicate otherwise. In the present study, total body water (TBW), total body lipid content, and plasma volume were measured in conscious DI rats and compared with corresponding values in weight-matched conscious Long-Evans (LE) rats. Fat content of DI rats (5.0 +/- 0.4 g/100 g body wt) was significantly lower than that of LE rats (7.6 +/- 0.6, P less than 0.005). TBW was not significantly different between the two strains whether expressed as milliliters per 100 g wet wt (DI 69.2 +/- 0.4 vs. LE 67.7 +/- 0.7) or as milliliters per 100 g fat-free wet wt (DI 73.4 +/- 0.5 vs. LE 73.3 +/- 0.4). Plasma volume of DI rats (4.4 +/- 0.1 ml/100 g body wt) was significantly higher than that of LE rats (3.9 +/- 0.2, P less than 0.025). Extracellular fluid volume was similar in the two strains although, for this measurement, the animals were neither weight- nor age-matched. Accordingly, the data indicate that under the conditions of this study the DI rat is not chronically volume contracted. It would appear that, given an adequate water supply, water balance can be achieved via the thirst mechanism, perhaps abetted by vasopressin-independent mechanisms of urine concentration.

Prostaglandin-dependent polyuria in hypercalcemia

The present experiments examined the role of prostaglandin biosynthesis in the increase in urine flow rate seen in rats with hypercalcemia induced by the administration of 1,25-dihydroxycholecalciferol. In a first group, rats receiving the vitamin D metabolite developed hypercalcemia, polyuria, and increased urine prostaglandin E excretion. Indomethacin resulted in a fall in urine prostaglandin E excretion. A second group was fluid restricted to ascertain whether increased thirst could be an etiologic mechanism of the polyuria. This resulted in a trivial fall in urine flow rate despite a fall in body weight and a rise in both urine and plasma osmolality. In a final group, prostaglandin inhibition restored the vasopressin sensitivity of the hypercalcemic kidney. Accordingly, the polyuria seen in hypercalcemic rats after the administration of 1,25-dihydroxycholecalciferol is associated with an increase in urine prostaglandin E excretion and can be reversed by inhibition of prostaglandin synthesis. In addition, this polyuria can occur independent of the thirst mechanism. Finally, there is evidence that the vasopressin resistance of the hypercalcemic kidney could be reversed by prostaglandin inhibition.