Absence Of Glycosuria Research Articles

Sodium-glucose co-transporter 2 inhibitors: mechanisms of renal action. Implications for diabetes and heart failure

The liver is not the exclusive site of glucose production in humans in the post-absorption state. Experimental data showed that the kidney is able of carrying out gluconeogenesis. Renal glucose production accounts for 20% of systemic glucose production. Evidence indicates that the kidney is able to reabsorb glucose from the glomerular filtrate through the sodium-glucose co-transporters (SGLT) 1 and 2 placed under the Bowman's capsule, in the thick portion of the proximal convoluted tubule, preserving this essential energy substrate for the organism. The maximal renal glucose reabsorption capacity (TmG), as well as the threshold for the spillover of glucose in the urine, are higher in diabetics than normal subjects and contribute to the hyperglycemic state in the absence of glycosuria. The administration of SGLT2 inhibitors in diabetics improves the excretion of sodium and glucose, reducing the threshold of glycosuria and TmG. This also restores the sodium concentration in the filtrate that reaches the macula densa (juxtaglomerular apparatus), which signals the appropriate perfusion of the kidney, defusing the secretion of renin and the activation of the neurohormonal axis that leads to the production of angiotensin II.Large clinical trials conducted with SGLT2 inhibitors in subjects with type 2 diabetes mellitus have demonstrated the great ability of this new class of drugs to achieve cardiac and renal benefits. All studies have shown SGLT2 inhibitors reduce the risk of hospitalizations for heart failure and the progression of kidney damage. A part of the favorable mechanisms is mediated by the natriuretic effect that is associated with the glycosuric effect, which reduces the activation of the renin-angiotensin-aldosterone system together with glomerular hyperfiltration.The aim of this review is to expand the knowledge among general cardiologists on the role of SGLT2 and SGLT1 in renal glucose homeostasis in healthy and diabetic subjects in the light of a potent class of drugs counteracting heart failure.

Characteristics and Impact Factors of Different Renal Glucose Thresholds in Patients with Type 2 Diabetes Mellitus in China

Background: The aim of this study was to assess the clinical features of different renal glucose threshold (RGT) groups with type 2 diabetes (T2DM) patients. Methods: A total of 2123 Chinese patients with T2DM hospitalized from Jan 2012 to Sep 2017 was collected in the study, including 174 patients with high RGT(defined as the absence of glycosuria when fasting plasma glucose (FPG) > 10 mmol/L), 111 patients with low RGT(defined as a the absence of glycosuria when FBG < 8 mmol/L) and 1838 patients with normal RGT. Results: Compared with normal RGT, patients with high RGT showed higher HbA1c, FPG, postprandial glucose (PPG) (P<0.001), triglycerides (TG) (P=0.008), total cholesterol (TC) (P=0.010) and urinary albumin creatinine ratio(UACR) (P=0.025), but lower Homeostatic Model Assessment of β cell (HOMA-β) (P=0.010), and were more likely to have diabetic peripheral neuropathy (DPN) (P=0.001). The high RGT group was composed of significantly more female patients (P<0.001). A logistic regression analysis showed that FPG and TG were negatively associated with normal RGT after adjusting for age, sex and BMI. Compared with normal RGT, low RGT patients showed lower FPG (P=0.023), and lower waist to hip ratio and uric acid(UA) (P<0.05) in female. A logistic regression analysis showed that FPG and UA were positively associated with normal RGT. Compared with low RGT, high RGT patients showed higher HbA1c, FPG, PPG, TG, TC (P<0.05) but lower HOMA-β(P=0.016), and were more likely to have DPN (P=0.010). The high RGT group was composed of significantly more female patients (P<0.001). A logistic regression analysis showed that FPG was negatively associated with low RGT. Conclusions: Our results indicate that the presence of T2DM subtypes characterized by different RGT. Patients with high RGT have higher glucose, TG and UACR levels, but lower levels of HOMA-β. HbA1c, FPG, TG, and UA were associated with RGT. Disclosure X. Huang: None. X. Gao: None. X. Cai: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Eli Lilly and Company, Bristol-Myers Squibb Company, Novartis AG, Novo Nordisk A/S, Merck & Co., Inc., Bayer AG, Merck Sharp & Dohme Corp., Takeda Development Center Asia, Pte. Ltd., Sanofi, Roche Pharma, Boehringer Ingelheim GmbH. Research Support; Self; AstraZeneca, Roche Pharma, Sanofi, Merck Sharp & Dohme Corp., Novartis AG, Eli Lilly and Company, Bristol-Myers Squibb Company.

PARACLINICAL MANAGEMENT REGARDING THE METABOLIC STATUS OF PATIENTS DIAGNOSED WITH TYPE 1 AND 2 DIABETES MELLITUS

Inflammatory processes, mineral imbalances and appearance of certain pathological compounds in urine are common phenomena in diabetes mellitus. We studied two groups of diabetic patients (inpatients and ambulatory specialty outpatients) during the first six months of 2017. Laboratory parameters concerning inflammation, mineral balance and urine analysis were evaluated, respectively we analyzed the scheme of treatment in case of inpatients. Based on our results we can affirm that in 25.51% of the studied diabetics the presence of an inflammatory process could be found. In 26.53% mineral imbalances could be observed, and in 69.69% we detected the presence of certain pathological compounds in urine, most often glycosuria. Significantly higher incidence of pathological compounds in urine could be observed in inpatients compared to outpatients. The vast majority of inpatients were treated with insuline (88.65%), oral antidiabetic therapy, especially metformin, being predominant in outpatients. In conclusion, we can state that in only 29.08% of the studied diabetic patients the laboratory analyses show lack of any inflammatory process, absence of glycosuria, respectively scarceness of mineral imbalance. Keywords: diabetes mellitus, glucose, neuropathy, hyperglycaemia

Promotion of Corneal Epithelial Wound Healing in Diabetic Rats by the Fibronectin-Derived Peptide PHSRN.

Topical application of the fibronectin-derived peptide PHSRN facilitates corneal epithelial wound healing in healthy animals and in patients with nonhealing epithelial defects. We have now examined the effect of PHSRN eye drops on the healing of corneal epithelial wounds in diabetic rats. Wistar rats were injected intraperitoneally with streptozotocin to induce diabetes or with a vehicle as a control. Four weeks after confirmation of the corresponding presence or absence of glycosuria, a 3-mm-diameter portion of the corneal epithelium of the right eye was excised and eye drops containing PHSRN (200 μM) or phosphate-buffered saline (PBS) vehicle were administered to the injured eye every 6 hours. The area of the epithelial defect did not differ significantly among the 4 experimental groups (diabetic or nondiabetic rats treated with PHSRN or vehicle) at 12 hours after wounding. At 18 hours, however, the area of the defect in diabetic rats treated with PHSRN (0.50 ± 0.34 mm) was significantly (P < 0.05) smaller than that in diabetic rats treated with PBS (1.06 ± 0.42 mm) and was similar to that in nondiabetic rats treated with PBS (0.60 ± 0.23 mm). The decrease in the size of the epithelial defect in diabetic rats treated with PHSRN was also found to be dependent on the dose of the peptide. Administration of PHSRN significantly facilitated healing of corneal epithelial wounds in diabetic rats, which suggests that PHSRN eye drops warrant further investigation as a treatment option for patients with diabetic keratopathy.

Remission from insulin dependence induced by continuous subcutaneous insulin infusion (CSII) in type I, newly diagnosed diabetics: role of some hormonal and immunologic factors.

Optimal and early control of recent onset, type I diabetes by intensive insulin therapy has been reported to allow insulin withdrawal in about two thirds of subjects treated. We used continuous s.c. insulin infusion (CSII) in the attempt to induce a temporary remission of insulin dependence in 18 newly diagnosed young adult diabetics. After 10 days of optimized glycometabolic control, insulin infusion was stopped and patients were switched to glibenclamide (15 mg/die) plus metformin (1 g/die). Diabetics were considered in remission of insulin dependence when their metabolic control fulfilled the following criteria for at least 3 months: absence of glycosuria, pre- and post-prandial blood glucose less than or equal to 120 and 180 mg/dl, respectively, HbA1c less than or equal to 7%. Insulin therapy could be discontinued for periods of over three months in 11 subjects (61%) and for as long as 18 months in one case. Insulin requirement during CSII was slightly higher in nonremitters (NR) than in remitters (R): 0.36-0.64 vs 0.26-0.41 U/kg/die. After 24 months from CSII, R still showed lower insulin requirement (0.35-0.42 U/kg/die) than NR (0.55-0.75 U/kg/die). Further, the role of some hormonal and immunologic factors was investigated. Plasma C-peptide and glucagon were measured, fasting and 2h after each meal, both on admission and immediately after CSII, when patients were switched to oral therapy. No difference in hormone levels could be detected on admission, whereas, after CSII, mean post-prandial increase of C-peptide over basal was significantly higher in R than in NR (1.18 +/- 0.37 vs 0.22 +/- 0.16 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocyte insulin binding and action in moderately obese NIDDM patients after dietary control of plasma glucose: reversal of postbinding abnormalities.

Studies of fat cells from patients with newly diagnosed, untreated non-insulin-dependent diabetes mellitus (NIDDM) have revealed severe abnormalities in insulin action on glucose transport and metabolism. To determine whether these defects can be reversed if good glycemic control is reached by dietary treatment, eight moderately obese NIDDM subjects were studied at diagnosis and again when the patients had been in good glycemic control induced by low-energy dieting for at least 2 mo (absence of glycosuria and fasting plasma glucose less than 7 mM). Average body weight decreased by 8 kg (P less than .05). Fasting plasma glucose decreased from 11.5 +/- 1.2 to 6.9 +/- 0.9 mM, whereas fasting serum insulin concentrations were unchanged. Adipocyte insulin binding at tracer concentration (15 pM, 37 degrees C) was not changed significantly (1.94 +/- 0.52 to 2.05 +/- 0.62% per 30 cm2 surface area/ml). The basal (non-insulin-stimulated) glucose transport (tracer glucose concentration 5 microM) increased from 25 +/- 12 to 44 +/- 14 pmol X 90 min-1 X 10 cm-2 surface area (P less than .02). The maximally insulin-stimulated glucose transport rate increased from 35 +/- 20 to 78 +/- 26 pmol/90 min (P less than .01). The percentage insulin response above basal levels increased from 31 +/- 40 to 89 +/- 58% (P less than .01). The insulin sensitivity (half-maximally stimulating insulin concentrations) was also improved (P less than .05). Glucose conversion rates to total lipids increased 34 +/- 62 and 65 +/- 80% in basal cells and maximally insulin-stimulated cells, respectively (.2 greater than P greater than .1, .1 greater than P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Normalization of estradiol receptor kinetics and hormonal activity in uterus of streptozotocin-induced diabetic rats treated with insulin.

In response to ip 17 beta-estradiol injection, ovariectomized streptozotocin-induced diabetic rats showed a decreased early and late stimulation of uterine protein synthesis as compared to nondiabetic controls. An early nuclear loss of estradiol-receptor complex and an accelerated estradiol clearance from the circulating blood were also observed in these animals. To establish whether these alterations in hormone kinetics and activity were related to the diabetic state, further investigation was done by treating diabetic animals with insulin, during 18 consecutive days after 3 to 8 months of long standing diabetes (type I treatment) or during 10 weeks starting immediately at the onset of the streptozotocin-induced disease (type II treatment). Both types of treatment either restored (type I) or preserved (type II) a normal body weight, low glycemia, and absence of glycosuria. Both types of treatment also restored a normal hormonal clearance so that higher plasma levels of estradiol at 30 and 90 min were noted after ip injection when compared to untreated diabetics. Nuclear retention of the estradiol-receptor complex was significantly higher in treated diabetics at 210 min as compared to the nondiabetic controls. Finally, stimulation of early protein synthesis at 90 min was normalized after both types of treatment. From the above observations it is concluded that insulin treatment restored a normal estrogen metabolism in diabetics, resulting in a prolonged retention of the estradiol-receptor complex in the uterine nuclei; the latter event in turn elicited a normal hormonal activity on protein synthesis. A direct influence of the diabetic state and of insulin treatment on the receptor kinetics and/or on the tissue response to the hormonal stimulus may however not be excluded.

Infantile rickets with server proximal renal tubular acidosis, responsive to vitamin D.

A variant of the Fanconi syndrome is reported in an infant with rickets, hypophosphataemia, severe `proximal9 renal tubular acidosis, and generalized hyperaminoaciduria. Noteworthy was the absence of glycosuria and cystinosis. Large doses of dihydrotachysterol (DHT) and of alkali controlled all of these abnormalities. Renal function tests including glomerular filtration rate, renal blood flow, ammonia secretion, titratable acidity, and bicarbonate handling were normal when the child was receiving DHT. At age 4½ years total relapse followed the cessation of therapy, and at this time serum parathyroid hormone levels were not raised. Now DHT alone (without alkali supplement) reversed all of the biochemical abnormalities including the acidosis. This child thus has an apparently vitamin D-dependent `proximal9 tubular acidosis, which is not due to secondary hyperparathyroidism.

INCREASED FREQUENCY OF DIABETES MELLITUS IN PATIENTS WITH HUNTINGTON'S CHOREA

Six of ten patients with documented Huntington's chorea had an unusual form of diabetes mellitus characterised by marked hyperglycæmia, resistance to ketosis, absence of glycosuria, and markedly elevated insulin levels in response to the administration of glucose or arginine. Four patients (group I) had normal fasting plasma glucose and insulin levels and a normal response to the glucose-tolerance test (G.T.T.). The other six (group II) had normal fasting glucose levels but slightly elevated fasting insulin levels; the G.T.T. was abnormal. In group I arginine resulted in normal glucose and insulin rise, and peak insulin at 30 minutes was 44·0±6·1 μU. per ml. In group II, despite a similar degree of glucose elevation after arginine, peak insulin at 30 minutes was 96·3±21·3 μU. per ml. Clinically no correlation other than duration of disease could be made with the metabolic findings. Whether these data may be explained by an abnormal genetic linkage between Huntington's chorea and carbohydrate intolerance, or by a primary imbalance of biogenic amines, is not yet established.

An unusual form of diabetes mellitus in ataxia telangiectasia.

Five of eight patients with documented ataxia telangiectasia had an unusual form of diabetes mellitus, characterized by marked hyperglycemia, resistance to ketosis, absence of glycosuria and markedly elevated plasma insulin levels in response to the administration of glucose or tolbutamide. Moreover, the blood glucose response to both exogenous and endogenous insulin was decreased, signifying insulin resistance similar to that found in pregnancy, acromegaly and obesity. In addition, the five subjects with diabetes had evidence of hepatic disease, which has not previously been reported in ataxia telangiectasia. Although the etiology of the hepatic dysfunction is not known, the immunologic deficiency commonly present in this disease may be responsible. Carbohydrate intolerance and the hypersecretion of insulin have been attributed to hepatic disease in some patients, or to certain lesions of the central nervous system in others, but it is not known if the diabetic state in ataxia telangiectasia results from dysfunction of either of these systems.

EFFECT OF ANGIOTENSIN 11 ON BLOOD GLUCOSE LEVEL IN THE DOG.

SummaryAngiotensin 11 given by intravenous infusion in a moderately large dose does not elevate either venous or arterial blood glucose levels within one hour in the conscious dog, nor does it produce glycosuria. This suggests that secondary release of catecholamines does not play a significant role in the physiological responses to angiotensin 11. The absence of glycosuria indicates that the renal tubular reabsorption of glucose was not affected by angiotensin 11 at this level of filtered load of glucose.

Diabetes insipidus; clinical and experimental studies with consideration of genetic relationships.

DIABETES insipidus was first differentiated from diabetes mellitus by Thomas Willis, in 1674. The term diabetes is derived from the Greek word for syphon, and insipidus differentiates this disease from mellitus, which connotes a honey taste. Diabetes insipidus has been defined as a chronic affection marked by extreme thirst, polyuria, nocturia, and an absence of glycosuria. In this study those affected with hereditary diabetes insipidus are referred to among their families by terms such as water topers, drinkers, drinking babies. It is a relatively rare condition seen in all ages and both sexes; however, it is noted more frequently in males than in females. The basis for this finding is demonstrated in the following study. CLASSIFICATION Clinically and etiologically diabetes insipidus is divided according to the following classification, the basis for which is presented in this study: Pituitary type: There is pituitary deficiency, in which the symptoms are relieved by

The influence of somatotropin and corticotropin on the islets of Langerhans of the rat.

THE manner in which the anterior hypophysis affects the islets of Langerhans in the rat is not clear. An increase in the amount of islet tissue has been reported to occur after the administration of a saline extract of the anterior hypophysis (Richardson and Young, 1937) and after hypophysectomy (Krichesky, 1936). Except for a preliminary observation that treatment with corticotropin may induce histological evidence of beta cell stimulation (Baker, 1952), no attention has been given to the cytological effects of individual pituitary hormones. The purpose of this report is (a) to describe the cellular changes induced in the islets by somatotropic and corticotropic preparations administered singly and in combination, and (b) to relate these effects to the presence or absence of glycosuria and to alterations in body weight and in the excretion of non-protein nitrogen. Clarification of the effects induced by somatotropin on the islets is particularly important because Young (1951) has postulated that an incre...

HEMOCHROMATOSIS

The following case is reported primarily because of (a) the absence of glycosuria and of significant decrease in dextrose tolerance in spite of the unusual quantity of iron in the liver and pancreas, (b) the absence of iron-containing pigment in the apparently characteristically pigmented skin, (c) the unusual complication of cutaneous xanthomatosis with hypercholesteremia in the absence of diabetes, (d) the antemortem demonstration of deficiency in adrenal cortical and androgenic hormones and (e) the unusual cause of death. REPORT OF CASE History. —S. S., a white Polish coal miner aged 45, was admitted to the service of Dr. H. A. Reimann, Jefferson Medical College Hospital, on Sept. 9, 1938, with the following complaints: (1) blue-gray discoloration of the skin (four years' duration), (2) intense itching (four years), (3) abdominal enlargement (three years) and (4) swelling of the legs (nine months). The family history and past medical history had no bearing

THE UTILIZATION OF JERUSALEM ARTICHOKES BY A PATIENT WITH DIABETES

The value of Jerusalem artichokes in the dietetic treatment of persons with diabetes mellitus depends on whether the absence of glycosuria is due to actual absorption and utilization of the carbohydrates or to escape from absorption. A patient of one of us has used large quantities of the dried Jerusalem artichoke in his diet for a number of years, and he volunteered to spend his spring academic vacation of 1926 at the New England Deaconess Hospital, subject to a controlled diet and to various physiologic and chemical observations designed to study this question. The previous literature with respect to the chemistry and metabolic effect of Jerusalem artichokes and inulin has been reviewed in a recent publication by Root and Baker. 1 They gave baked artichokes containing from 31 to 81 Gm. of carbohydrate in six cases and determined the respiratory exchange by the gasometer method, finding a rise in respiratory quotients

Experimental diabete gras

French authors, especially Lancereaux,1 have described two types of diabetes mellitus: diabete maigre and diabete gras. Lancereaux believed that the former was due to pancreatic disease; diabetes with obesity, according to him, was not of pancreatic origin. Although most clinicians maintain that it is impossible to recognize the sharp distinction between diabete maigre and diabete gras, yet the fact remains that the physician in the majority of cases sees either lean or stout diabetics.Diabetic children and young adults are usually lean, from the beginning of the disease until exitus. According to Joslin,2 obesity is a marked feature of diabetes in the fifth and sixth decade of life. One must admit that while diabete gras may ultimately turn into diabete maigre, the latter condition rarely is transformed to the former.Clinically three varieties of diabete gras may be distinguished:1. Obesity associated with excretion of sugar in the urine.2. Obesity with hyperglycemia in the absence of glycosuria.3. Obesi...

Experiences with thyroidectomy and ligation of the thyroid arterie in depancreatized dogs

The absence of glycosuria and the high sugar tolerance in myxoedematous individuals led us to undertake the experiments cited in this brief report.Dog No. 100, male, weight 14 kilo., partial pancreatectomy performed January 12, 1921. Urine positive for sugar the following day. It persisted in amounts of from 2 to 3 per cent. until January 19, when both inferior thyroid arteries were ligated. Glycosuria continued until January 26, 1921, when complete thyroidectomy was done, sparing the parathyroids. Urine became negative for sugar on the following day and continued so. On February 5, 1921, with blood sugar 95 mgms. an additional 3.4 gms. of pancreatic tissue was removed with no change in the urinary findings. On February 9, blood sugar was 86 mgms. On this day 150 gms. glucose were introduced by the stomach tube. Tests for urinary sugar remained negative. On May 9, rest of the pancreas, amounting to 10 gms. was removed. Urine continued negative for sugar until May 14, when intestines prolapsed through woun...

THE CONTROL OF ACIDOSIS IN THE TREATMENT OF DIABETES

INTRODUCTION During the past five years marked advances have been made in the treatment of diabetes, due largely to the introduction by Allen of the method. In the practical application of this method of treatment the patient is fasted until glycosuria disappears; and subsequent to the initial fast, fasting is employed to such an extent as is necessary to aid in keeping the patient free from glycosuria. In other words, the most important and significant sign or symptom by which the therapeutic regime is regulated is the presence or absence of sugar in the urine. Allen, however, has emphasized the fact that in diabetes a disturbance of the entire metabolic mechanism of the body is present, and that the presence or absence of glycosuria at any given time is but a crude test of the state of that function, though practically it is the best test available. In the