Alimentary Hyperglycemia Research Articles

The Hypoglycemic Activity of Lactic Acid Bacteria Isolated From Medicinal Plants of Uzbekistan and Their Probiotic Potential

The study aimed to evaluate the hypoglycemic activity of lactic acid bacteria isolated from the medicinal plants possessing antioxidant and hypoglycemic properties growing in Uzbekistan and analyze their prоbiotic properties.
 Four plant isolates of lactic acid bacteria (LAB) and three commercial strains were used in the study. Alimentary hyperglycemia was induced in white outbred rats, and glucose level was measured before and after treatment with lactic acid bacteria according to the experiment scheme using an intraperitoneal glucose tolerance test.
 The investigation was shown that strains of Lactobacillus kunkeei 1, L. рlantarum TK1, L. рlantarum KA3, Enterococcus faecium effectively reduce postprandial hyperglycemia in rats. Moreover, evaluation of their probiotic properties: sensitivity to antibiotics, simulated gastric juice, simulated juice of small intestine, bile, and elevated concentration of sodium chloride, demonstrated that the strains Enterococcus faecium 1, Lactobacillus kunkeei 1, L. рlantarum TK1, L. рlantarum KA3 meet the criteria for probiotics.
 These strains could be considered promising candidates for the preparation of probiotic preparations intended not only to correct gut microbiota but also to maintain normal blood glucose levels.

Determination of hypoglycemic activity of the herbal mixtures in screening study

Diabetes mellitus is an important social and medical problem, as it causes the development of dangerous complications that lead to disability and mortality. This disease is characterized by a multi-vector pathogenesis that requires a comprehensive approach to treatment. Due to the using of medicinal plantsmixtures in the treatment of diabetes, it is possible to cover many aspects of the development of this disease and its complications.The aim of the study was to evaluate the hypoglycemic activity of some herbal mixtures and to establish their conditionally therapeutic doses on normoglycemic rats by glucose load tests.The study was performed on male albino rats weighing 180–200 g, which for preventive treatment during 20 days orally received aqueous extracts (1:10) of the studied herbal mixtures at a dose 6 mL/kg/day, 9 mL/kg/day and 12 mL/kg/day and comparison drugs – the official herbal mixtures «Arfazetin» at adose 9 mL/kg/day and metformin tablets at a dose 60 mg/kg/day. The study of hypoglycemic properties and the establishment of a conditional therapeutic doses was carried out using glucose loading tests (OGTT and IPGTT). All experiments were performed in accordance with general ethical principles and therecommendations of the EEC Council directive 2010/63/EU about the protection of animals, which are used for scientific purposes.The results of the study showed that the 20-day preventive administration of the herbal mixtures reduced alimentary hyperglycemia at the 30th min of OGTT and helped regulate carbohydrate tolerance disorders by reducing hyperglycemia at the 15th min of IPGTT. The highest hypoglycemic activity showedthe herbal mixture № 19 (Urticae folia, Taraxaci radice, Myrtilli folia, Rosae fructus and Menthae folia) at a dose 12 mL/kg/day, which was almost on a par with the comparison drug – metformin tablets, but exceeded the official herbal mixture «Arfazetin». In addition, the dose-dependence of the effectiveness of all five studied herbal mixtures was established.

The screening study of the hypoglycemic activity of herbal mixtures (presentation 3)

Diabetes mellitus is an important social and medical problem as it causes the development of dangerous complications leading to disability and mortality. This disease is characterized by a multi-vector pathogenesis that requires a comprehensive approach to the treatment. Due to the use of mixtures of medicinal plants in the treatment of diabetes it is possible to cover all aspects of the development of this disease and its complications.Aim. To study the hypoglycemic activity of herbal mixtures used in folk medicine for the prevention and treatment of diabetes mellitus type 2, and determine their conditional therapeutic dose.Materials and methods. The study was performed on male albino rats weighing 180-200 g. For the preventive treatment within 20 days they received orally the aqueous extracts (1:10) of the herbal mixtures studied in the doses of 6 mL/kg/day, 9 mL/kg/day and 12 mL/kg/day and the reference drugs – the official herbal mixture “Arfazetin” in the dose of 9 mL/kg/day and metformin tablets in the dose of 60 mg/kg/day. The study of hypoglycemic properties and determination of the conditional therapeutic dose of the mixtures studied were performed using glucose loading tests (oral glucose tolerance test – OGTT and intraperitoneal glucose tolerance test– IPGTT). All experiments were performed in accordance with general ethical principles with the recommendations of the EEC Council Directive 2010/63/EU about the protection of animals used for scientific purposes.Results and discussion. The results of the study showed that the 20-day preventive treatment with the herbal mixtures reduced alimentary hyperglycemia 30 minutes after OGTT and regulated carbohydrate tolerance disorders by reducing hyperglycemia 15 minutes after IPGTT. The herbal mixture No. 13 in the dose of 12 mL/kg/day showed the highest hypoglycemic activity, which was almost similar with the reference drug – metformin tablets, but exceeded the official herbal mixture “Arfazetin” by its efficiency. In addition, the dose-dependence of the effectiveness of all five herbal mixtures studied was determined.Conclusions. For the first time, the screening study of the hypoglycemic activity of herbal mixtures used in folk medicine for the prevention and treatment of diabetes mellitus type 2 has been conducted. It has been determined that the herbal mixture No. 13 containing Cichorii radices, Elymi repens rhizomata, Helichrysi arenarii flores, Rosae fructus, Maydis style cum stigmatis shows the highest effectiveness by the ability to reduce alimentary hyperglycemia during OGTT and reduce impaired carbohydrate tolerance during IPGTT. Its conditional therapeutic dose, which is 12 mL/kg/day, has been determined.

Screening of hypoglycemic activity of herbal mixtures (message ІІ)

Topicality. Diabetes mellitus is an important social and medical problem, as it causes the development of dangerous complications that lead to disability and mortality. This disease is characterized by a multi-vector pathogenesis that requires a comprehensive approach to treatment. Due to the use of mixtures of medicinal plants in the treatment of diabetes, it is possible to cover all aspects of the development of this disease and its complications. In addition, the niche of the pharmaceutical market of Ukraine with phytomixtures is almost empty.Aim. To study the hypoglycemic activity of the herbal mixtures, which are used in folk medicine for diabetes mellitus type 2 prevention and treatment, but do not have a scientific basis and to establish their conditional therapeutic dose.Materials and methods. The study has been performed in male albino rats weighing 180-200 g, during 20 days they have been receiving orally for preventive treatment aqueous extracts (1:10) of the studied herbal mixtures at a dose 6 mL/kg/day, 9 mL/kg/day and 12 mL/kg/day and comparison drugs – the official herbal mixtures “Arfazetin” at a dose 9 mL/kg/day and tablets metformin at a dose 60 mg/kg/day. The study of hypoglycemic properties and the establishment of a conditional therapeutic dose of the studied mixtures was carried out using glucose loading tests. All experiments have been performed in accordance with general ethical principles with the recommendations of the EEC Council directive 2010/63/EU about the protection of animals used for scientific experiment.Results and discussion. The results of the study showed the 20-day preventive treatment by the herbal mixtures reduced alimentary hyperglycemia at the 30th minutes of OGTT and helped regulate carbohydrate tolerance disorders by reducing hyperglycemia at the 15th minutes of IPGTT. The highest hypoglycemic activity showed the herbal mixture No. 7 in a dose 12 mL/kg/day, which was almost on a par with the comparison drug – tablets metformin, but exceeded the official herbal mixture “Arfazetin”. In addition, the dose-dependence of the effectiveness of all five studied herbal mixtures was established.Conclusions. For the first time, it was conducted the screening study of hypoglycemic activity of the herbal mixtures, which are used in folk medicine for the prevention and treatment of diabetes mellitus type 2. It was determined that the greatest effectiveness in terms of the ability to reduce alimentary hyperglycemia during OGTT and reduce impaired carbohydrate tolerance during IPGTT show the herbal mixture No. 7, which includes Inulae rhizomata et radices, Helichrysi arenarii flores, Maydis style cum sigmatis, Origani herba, Rosae fructus, Taraxaci radices. It was established its conditional therapeutic dose 12 mL/kg/day.

Screening study of hypoglycemic activity of the herbal mixtures (message 1)

The aim. To study the hypoglycemic activity of the herbal mixtures, which are used in folk medicine for the prevention and treatment of diabetes mellitus type 2, but do not have a scientific basis and to establish their conditional therapeutic dose.Materials and methods. The study was performed on male albino rats weighing 180-200 g, which for preventive treatment during 20 days orally received aqueous extracts (1:10) of the studied herbal mixtures at a dose 6 mL/kg/day, 9 mL/kg/day and 12 mL/kg/day and comparison drugs – the officinal herbal mixtures “Arfazetin” at a dose 9 mL/kg/day and metformin tablets at a dose 60 mg/kg/day. The study of hypoglycemic properties and the establishment of a conditional therapeutic dose of the studied mixtures was carried out using glucose loading tests. All experiments were performed in accordance with general ethical principles with the recommendations of the EEC Council directive 2010/63/EU about the protection of animals, which are used for scientific purposes.Results. The results of the study showed that the 20-day preventive treatment by the herbal mixtures reduced alimentary hyperglycemia at the 30th minutes of OGTT and helped regulate carbohydrate tolerance disorders by reducing hyperglycemia at the 15th minutes of IPGTT. The highest hypoglycemic activity showed the herbal mixtures No. 3 (12 mL/kg/day) and No. 4 (12 mL/kg/day), which was almost on a par with the comparison drug –metformin tablets, but exceeded the officinal herbal mixture “Arfazetin”. In addition, the dose-dependence of the effectiveness of all five studied herbal mixtures was established.Conclusions. For the first time, it was conducted the screening study of hypoglycemic activity of the herbal mixtures, which are used in folk medicine for the prevention and treatment of diabetes mellitus type 2. It was determined that the greatest effectiveness in terms of the ability to reduce alimentary hyperglycemia during OGTT and reduce impaired carbohydrate tolerance during IPGTT show the herbal mixtures No. 3 (which includes Urticea folia, Cichorii radices, Rosae fructus, Elymi repens rhizomata, Taraxaci radices) and No. 4 (which includes Arctii lappae radices, Elymi repens rhizomata, Maydis style cum sigmatis, Helichrysi arenarii flores, Rosae fructus). It was established their conditional therapeutic dose of 12 mL/kg/day

Calcium Channel Blockers Inhibit the Hyperglycemic Effect of Calcitonin

We studied the effect of Russian preparation of porcine calcitonin (calcitrin, 1 U/100 g) and blockers of Ca(2+) channels nifedipine (1 mg/kg, blocker of chemosensitive Ca(2+) channels) and isoptin (5 mg/kg, blocker of voltage-dependent Ca(2+) channels) on glucose metabolism. Calcitonin produced a pronounced hyperglycemic effect in rats. A close negative correlation was found between glucose level and total calcium content. Injection of calcitonin reduced glucose tolerance in rats. Isoptin and nifedipine reduced plasma calcium level and did not affect significantly the blood glucose levels, did not change the pattern of alimentary hyperglycemia in response to glucose load, completely abolished the hyperglycemic effect of calcitonin, and prevented calcitonin-induced impairment of glucose tolerance.

Mechanisms involved in the coordinate regulation of strategic enzymes of glucose metabolism

In this review, we evaluate the relative regulatory importance of specific strategic enzymes (in particular glycogen synthase, acetyl-CoA carboxylase [ACC] and the pyruvate dehydrogenase complex [PDH]) for carbohydrate utilization as an anabolic precursor and as an energy substrate during the nutritional transitions between the fed and fasted states. The involvement of the specific protein kinases contributing to the inactivation of these enzymes by phosphorylation [cyclic AMP-dependent protein kinase, AMP-activated protein kinase and PDH kinase] in achieving each regulatory response is also assessed. We demonstrate a striking temporal correlation between hepatic glycogen mobilization and PDH and ACC inactivation by phosphorylation during the immediate postabsorptive period; in contrast, rates of hepatic glycogen synthesis and PDH and ACC expressed activities do not change in parallel during refeeding. The results are consistent with shifting of the primary sites of control for overall hepatic carbon flux during the fed-to-starved and starved-to-fed nutritional transitions achieved, at least in part, by a complex pattern of regulation by protein phosphorylation and metabolites which is critically dependent on the precise nutritional status. Data are also presented that demonstrate asynchronous suppression of glucose uptake/phosphorylation and pyruvate oxidation in cardiac and skeletal muscle during progressive starvation. Analogous asynchrony is observed in the reactivation of these processes in cardiac and skeletal muscle during refeeding after starvation. We provide evidence in support of the concept that selective suppression of pyruvate oxidation in oxidative muscles during early starvation and during the initial phase of refeeding is achieved because of differential sensitivity of glucose uptake/phosphorylation and pyruvate oxidation to lipid-fuel utilization. We discuss the relative importance of regulatory events governing local fatty acid production and utilization (via lipoprotein lipase and carnitine palmitoyltransferase 1, respectively) or overall fatty acid supply (dictated by events at the adipocyte) for fuel utilization by muscle during nutritional transitions. Finally, we assess the regulatory importance of glycogen synthesis in determining overall rates of glucose clearance by skeletal muscle during alimentary hyperglycemia and hyperinsulinemia.

Pancreatic endocrine responses to physiological changes in plasma neurotensin concentration in the calf.

1. Plasma neurotensin concentration was found to increase by between 3 and 18 pmol/l 20 min after feeding in conscious 2-6 week old calves. 2. Synthetic bovine neurotensin was infused I.V. at a dose which reproduced the rise in the plasma concentration (1 pmol. kg-1 min-1), in calves of the same age, which were also receiving a continuous I.V. infusion of glucose (0.03 mmol. kg-1. min-1) to mimic alimentary hyperglycaemia. Under these conditions neurotensin caused a significant rise in the mean concentration of both insulin and pancreatic polypeptide (PP), but not that of glucagon, in the arterial plasma. 3. The rise of plasma insulin concentration, but not that of PP, in response to the same dose of neurotensin was strongly potentiated during infusions of exogenous amino acids. There was also a significant rise in plasma glucagon concentration in response to neurotensin in the calves given amino acids. 4. It is concluded that neurotensin is a physiological incretin in the calf.

The role of the autonomic nervous system in the control of pancreatic endocrine responses to milk ingestion in the calf.

1. Pancreatic endocrine responses to ingestion of milk have been investigated in conscious unweaned calves, 3-5 weeks after birth. Passage of gastric content from abomasum to small intestine was prevented by means of a cannula placed in the duodenum adjacent to the pylorus and food was witheld for at least 22 h in order to deplete liver glycogen. 2. Under these conditions ingestion of milk was followed by a prompt rise in the concentrations of pancreatic glucagon, PP and gastrin in the arterial plasma but the usual rises in plasma glucose and insulin concentration were absent. 3. Evidence was obtained to show that absorption of glucose from the small intestine occurs sufficiently rapidly to account for the initial rise in plasma glucose concentration after feeding in normal animals. However, the rise in plasma glucagon concentration was sufficient to contribute to alimentary hyperglycaemia by promoting hepatic glycogenolysis in calves with abundant liver glycogen. 4. None of the neuroendocrine responses to ingestion of milk was affected by prior section of the splanchnic nerves whereas each was blocked by atropine (0.2 mg/kg), showing that all depend upon muscarinic, parasympathetic rather than sympathetic activity, in the absence of extraneous stress.

Morphological and histochemical changes in the rabbit aorta in exogenous and endogenous hyperglycemia

Alimentary hyperglycemia and insulin deficiency were accompanied in rats by atherosclerotic affection of the aorta whose degree increased in feeding of cholesterol to such animals. The detected morphological and histochemical changes in the wall of the aorta correlated with the biochemical atherogenic shifts in the blood serum of the corresponding animals groups established earlier.

Role of alimentary hyperglycemia in the pathogenesis of some disturbances of lipid metabolism

In experiments on cats and dogs under general anesthesia nonachlazine, a new antianginal agent, depressed the reflex decrease of the blood flow to the coronary arteries (electromagnetic recording). Nonachlazine also depressed the reflex decrease of the blood flow in the system of common carotic artery, and the pressure vasomotor reflexes. During recording the tonic and reflex activity in the heart sympathetic nerves nonachlazine proved to selectively inhibit the vasoconstrictor impulses from Adelta-afferent fibers of the spinal nerves, that is it influenced the vasomotor component of the "primary" pain reaction. This mechanism could underlie the block by nonachlazine of the pain syndrome during the heart ischemia disease.

Gastric Operations and Glucose Homeostasis: II. Glucagon and secretin

Alimentary hyperglycemia in patients who have undergone gastric operations may be due, in part, to altered intestinal signals for glucose disposition. We measured glucose, immunoreactive insulin (IRI) pancreatic glucagon (IRG), and glucagon-like immunoreactivity (GLI) after oral glucose in patients with prior antrectomy or vagotomy and pyloroplasty and in normal individuals. All subjects had normal assimilation coefficients for intravenous glucose, which suggests that the responsiveness of the pancreatic beta-cells had not been altered by the surgical procedures. The early hyperglycemic response to oral glucose and the associated elevation of plasma GLI were much greater and the IRI levels slightly higher in both experimental groups in comparison to normal subjects. A decrease in the level of IRG, albeit not statistically significant, was noted in all groups after the ingestion of glucose. In gastrectomy patients, secretin infusion during repeated oral glucose tolerance tests partially corrected the hyperglycemia and lowered plasma GLI and IRI levels. The responses of the vagotomy and pyloroplasty patients and of the normal subjects were not altered by secretin infusion. We conclude that the intolerance or oral glucose after gastric surgery may be related to elevated GLI levels, and that the beneficial effect of secretin may be due to its ability to decrease these levels.

Further Observations on the Blood Glucose Level inChanna punctatus(Bloch.)

There is a significant rise in the blood glucose level of Channa punctatus following surgical extirpation of the principal islets. The hyperglycemia persists for nearly 30 days in the isletectomized fish. A transient hyperglycemia is exhibited by the sham operated control fish also. If the isletectomized fish are force-fed, a further increase in the blood glucose level is obtained. The force feeding of normal, unoperated fish results in an alimentary hyperglycemia at about 10–24 hours post-prandial.

Intraocular Pressure in Juvenile Diabetics

The relationship of the blood sugar to in­ traocular pressure has excited considerable controversy since Heine, in 1903, and Krause, in 1904, reported hypotonia of the eye in diabetic coma. In these cases, the in­ traocular pressure returns to normal when the blood sugar levels are brought into the normal range by the administration of insu­ lin. A fall in the intraocular pressure in dia­ betics during hypoglycemia has been report­ ed by Richter and Weichman and Koch. Schmidt, Toth and others have reported that, in nondiabetics, there is no lowering of the intraocular pressure during induced hy­ poglycemia. Martin found the variations in the intra­ ocular pressure over 24 hours larger and more irregular in diabetics than in nondia­ betics. He was not able to correlate these variations with fluctuations in the blood sugar levels. However, Poos was able to correlate such variations in the intraocular pressure with fluctuations in the bloodsugar values. Larsen and Poulsen were able to demon­ strate that, during severe hypoglycemia, the intraocular pressure fell abruptly. They were also able to show that, in diabetics with reti­ nopathy, a fall in the intraocular pressure occurred during alimentary hyperglycemia, whereas in diabetics without retinopathy no drop in the intraocular pressure occurred during alimentary hyperglycemia. In 1964, Safir and associates reported an increase in the intraocular pressure in a

CARBOHYDRATE INTOLERANCE IN POSTGASTRECTOMY PATIENTS

Whenn oral glucose tolerance test is done on a subject who has had a gastric operation for peptic ulcer, an abnormal response may be obtained. The blood glucose curve shows a rapid rise to abnormally high levels and then a fall to normal or to hypoglycemic levels after two hours. Symptoms of hypoglycemia may occur during the phase of falling blood glucose levels. This type of response, often referred to as the lag curve or the curve of alimentary hyperglycemia, may also be observed in otherwise healthy individuals or in thyrotoxic patients. If such a curve is found in a healthy patient, periodic retesting is advisable to detect possible progression to a diabetic curve. The cause of the lag curve in postgastrectomy patients is presumed to be the rapid absorption of glucose from the jejunum secondary to rapid transit from the stomach. If this were so, then there would be

Carbohydrate Intolerance in Postgastrectomy Patients

AFTER a gastric operation for peptic ulcer many patients show an abnormal response to an oral glucose tolerance test.1The blood sugar curve obtained during a test is characterized by a rapid rise to an abnormally high level and then a fall to normal, or to hypoglycemic levels, at two hours. The fall in blood sugar levels may be accompanied by hypoglycemic symptoms.2This type of blood sugar curve has been called the lag curve,3or the curve of alimentary hyperglycemia. It is usually attributed to the rapid absorption of glucose in the jejunum, secondary to rapid transit from the stomach. This curve is not confined to those who have had a gastric operation, however, for it may be found in otherwise healthy people, or in thyrotoxic patients. LeQuesne and co-workers4studied carbohydrate metabolism and plasma volume changes in patients who developed the dumping syndrome after

Lack of Influence of Insulin-induced Hypoglycemia on Alimentary Hyperglycemia

Studies were designed to determine the effect, in diabetic patients, of insulin induced hypoglycemia upon alimentary hyperglycemia. The following results were obtained. 1. In a four-hour study, as a control day, each of four patients was given his usual insulin one hour before the oral administration of 100 gm. of glucose. On another occasion, under identical conditions, hypoglycemia was produced during the hour preceding glucose administration, by intravenous administration of Crystalline Insulin. There was no greater impairment of glucose tolerance during the subsequent three hours than noted in the control study. 2. In ten patients, maintained on constant diets for three consecutive days, blood sugars were determined at frequent intervals from 7 a.m. to 10 p.m. each day. Each patient, if insulin dependent, received his usual dose before breakfast on all three days. On the second day the administration of additional subcutaneous Crystalline Insulin produced hypoglycemia during the forenoon. No carbohydrate supplementation was given and generally the hypoglycemia was corrected only by lunch given at the usual time. The postprandial blood sugar elevations for the balance of that day and throughout the third day were no greater than those of the first or control day. 3. In one patient six identical studies were performed. In each instance 25 gm. of glucose was given by mouth at 7 a.m. on each of three consecutive days. Blood sugars were measured at two-hour intervals from 8 a.m. to 12 noon. On day two hypoglycemia was produced by the administration of 15-25 U. Crystalline Insulin after the 8 a.m. blood specimen was drawn. Although mean blood sugars were statistically significantly higher on day three than on day one at 8 a.m. and 12 noon, the quantitative measurement of urine sugar showed no increase over that of the control day on either the day of hypoglycemia or the following day. These data do not support the concept, in patients with diabetes mellitus, that hypoglycemia is followed by further impairment of glucose tolerance.

Effects of tolbutamide on intestinal glucose absorption and blood glucose levels.

SummaryIn rats glucose absorption from the small intestine was not affected by the presence of tolbutamide in the glucose solution used. The tolbutamide absorbed in these experiments was sufficient to produce a relative suppression of the alimentary hyperglycemia present at the end of the absorption period.

CLINICAL STUDIES ON ATP (ADENOSINE TRIPHOSPHATE)

In diabetic patients (41 adults), the effect of ATP injection on the carbohydrate metabolism was compared with insulin action. The results were summarized as follows. 1) By administration of ATP, blood sugar levels in diabetic patients were usually reduced, but these levels in normal subjects were unchanged by ATP administration. 2) In many cases, alimentary hyperglycemia in diabetic patients was controlled by administration of ATP, and hypoglycemic effect of insulin was raised when ATP was injected with insulin. 3) Serum inorganic phosphorus were reduced by administration of ATP and the reducing-ratio of phosphorus by intravenous injection of glucose was intensified by administration of ATP. 4) Blood pyruvic acid levels were raised by insulin injection. On the contrary, blood pyrubic acid levels were reduced by ATP injection, and the elevation of blood pyruvic acid levels by intravenous injection of glucose was also controlled by ATP injection. 5) Blood lactic acid levels were reduced by ATP injection and the elevation of lactic acid levels by intravenous injection of glucose was controlled by ATP.

Suprarenal tumor (Cushing's syndrome)

T HE ease of this patient is reported because he had bilateral suprarenal tumors, but he did not conform completely to the clinical picture as described by Albright. The obesity was marked and developed rapidly, but was definitely associated with an excessively abnormal appetite; the fat accumulation involved not only the face, neck, trunk, and abdomen, but also the extremities. The muscular weakness was not marked; the osteoporosis was of moderate degree. In contradistinction to impotency, this boy had precocious puberty and virilism. Tumors of the suprarenal gland produce a definite well-known entity conveniently called Cushing's syndrome. The literature is replete with ease reports of this condition and exhaustive studies have been made. In Albright 's second paper on the subject he specified certain clinical manifestations and states that t he diagnosis would be questionable in any ease which did not have the first three of these manifestations. They are: (1) diabetes, which is usually mild and often only demonstrable as the responsiveness to an alimentary hyperglycemia (i.e., decreased sugar tolerance), but which is resistant to insulin; (2) muscular weakness, with a low creatinine excretion as an indication of decreased muscle mass; (3) osteoporosis, especially of the spine (not to be confused with osteitis fibrosa generalisata or with osteomalaeia since the serum phosphatase level is normal rather than high), associated with hyperca]cinuria ear]y in the disease and, in many instances, with nephrolithiasis; (4) a thin, reddish (?) (transparent) skin, easy bruisability, often large purplish striae, a marked susceptibility to skin infection; (5) impotence in men and amenorrhea in women; (6) mild to moderate obesity, with a tendency f o r the fat to be deposited in the neck and face (mostly in the face) and to spare the extremities; (7) mild hirsutism without other evidence of virilism (clitoris not enlarged, thyroid eartilage and voice normal in females), usually but not always associated with a slight to moderate elevation in the urinary excretion of the 17-ketosteroids; (8) mild erythroeytosis (red count circa 5.8 M) without increased blood volume; (9) hypertension and arteriosclerosis often accompanied by coronary heart disease and vascular disease of the kidneys. ''1 This paper presents a thorough study of the problem. Among the other papers there were thirtythree well-studied cases presented by Kttowlto~ 2 in 1953. The electrolyte disturbances in Cushing's syndrome were reviewed by Sprague and Power a in 1953. Subtotal adrenalectomy for Cushings syndrome was re-