ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12856.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract.The carboxylic acid balance of perfused livers from normal and streptozotocin diabetic rats (in insulin treatment or deprived of insulin for various time intervals) was determined by measurement of FFA, lactate, pyruvate and in ketone bodies in input and output medium. In livers from fed rats of either type of treatment, the carboxylic acid balance was close to zero, and the same was true for livers from 48‐hour fasting rats after 6 hours or more of insulin deprivation. Thus, when livers were perfused with a medium containing 1 mM of lactate and of FFA, the diabetic state did not turn the liver into a state of net acid production. Addition of a high concentration of glucose to the medium inhibited the rate of ketogenesis significantly in livers from fasting diabetic animals perfused for 6 hours after discontinuation of insulin treatment. In this way a high glucose concentration caused an increased net uptake of carboxylic acid in such livers. A decrease in the liver blood flow to one‐third of the normal invariably turned livers into a state of net acid production due to (a) a strongly diminished uptake of lactate in livers perfused with a medium containing no glucose and (b) by a large net lactate production in livers perfused with 20 mM glucose. On the basis of these observations and of data from available literature it is suggested that the pathogenesis of the diabetic ketoacidosis in humans can be divided into two phases: 1) An initial phase (pH 7.4 to 7.1) distinguished by a gradually increasing accumulation of acid equivalents in the body largely caused by accumulation of the keto acids (3‐hydroxybutyrate and acetoacetate) and of non‐carbonic acid equivalents originating from the excretion in the urine of ketone bodies as bases, i.e. with sodium and potassium as the corresponding cations which ensure electroneutrality. 2) A late phase (π<7.1) distinguished by severely impaired capacity for renal excretion of acid equivalents, of an impaired capacity for respiratory compensation of the metabolic acidosis and by a changed hepatic metabolism of lactate: from a net lactate clearing function the liver is turned into a net lactate producing function due to a low perfusion flow and a high glucose concentration. Thus, in the late phase the organism has lost any possibility to eliminate acid. On the basis of pKa values for the second acid group of organic phosphates and inorganic phosphate the estimate is given that net hydrolysis of organic phosphates, which takes place during the development of diabetic ketoacidosis, will rather cause a net removal than a net supply of non‐carbonic acid to the b

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12857.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

ABSTRACT.Determination of glycosylated hemoglobin, HbA1, has become of great interest in diabetic patients as the values seem to reflect mean blood glucose values over longer periods of time. Several methods for determination of HbAlare now available. We have used a microchromatographic procedure which seems suitable for routine clinical work. In 94 healthy subjects HbA1was 6.5±0.8% (mean ± S.D.). The corresponding value obtained in 126 diabetics was 9.6±1.8%. Particularly in patients treated with insulin HbA1‐determinations are of value for assessment of the carbohydrate state, since in these patients the glucose values are prone to great variations. The exact relationship between the HbA1‐values and the mean blood glucose level might vary between patients, however. Thus erythrocyte survival and renal function may influence the HbA1‐values and more experience is needed in the interpretation of values. Nevertheless, preliminary data from a study in progress support the expectation that HbA1‐determinations are likely to become a valuable adjunct in the routine management of diabeti

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12858.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12859.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

ABSTRACT.Glucagon and metabolic responses to insulin‐induced hypoglycemia were studied in seven juvenile diabetics, age 31±2 years (mean and S.E.M.), duration of diabetes 17±3 years, with diabetic autonomic neuropathy (decreased beat‐to beat variation in heart rate during hyperventilation and/or orthostatic hypotension) and in seven control patients of similar age and duration of diabetes without neuropathy. Before the hypoglycaemic episode, normoglycemia had been maintained for at least 10 hours. Following hypoglycemia, a slight but significant and similar increase in plasma glucagon was found in both patient groups. Metabolic responses to hypoglycemia were also similar in the two patient groups. In conclusion, diabetic autonomic neuropathy has no effect on glucagon and metabolic responses to hypoglycemia in juvenile, insulin‐treated di

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12860.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12861.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

ABSTRACT.Radioimmunoassays (RIA) for C‐peptide and proinsulin have been developed and their sources of error investigated. Immunoreactive insulin (IRI), C‐peptide and proinsulin were determined prior and up to 3 hours after glucose load in 13 non‐diabetics. Fasting proinsulin constituted 35% of the IRI (μU/μU), but the proportion of proinsulin increased at 2 and 3 hours to about 47 % and 70%. Since this percent depends on the reactivity of proinsulin in the insulin RIA an improved method of expressing the relationship between proinsulin and insulin was used. The insulin concentration (IRI μU/ ml—proinsulin μU/ml) was determined and the molar ratio between proinsulin: insulin calculated. It was 0.83±0.45 at fasting and 0.28±0.14 at 15 min. At 1.5 hours the ratio was 1.30±0.78 and continued to rise in most persons. Proinsulin: C‐peptide was 0.051 at fasting, not changing much during the first hour, after which the ratio increased to 0.113 and 0.141 at 2 and 3 hours, respectively. Thus proinsulin may be secreted in increasing quantities as compared to insulin and C‐peptide in the late phase of a heavy oral glucose load. The B‐cell activity in insulin treated diabetics may be evaluated by C‐peptide determinations. In serum with insulin antibodies, bound proinsulin has to be removed prior to C‐peptide determination to avoid falsely high C‐peptide estimates. The most simple method is a PEG precipitation of the antibody complexes. C‐peptide is then estimated in the 12.5% PEG‐containing supernatant. It was found to be important to prepare the standards in 12.5%

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12862.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12863.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12864.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

ABSTRACT.Eight attempts at segmental pancreatic transplantation were made in 6 diabetic patients. While the indications for transplantation differed all the patients were severely incapacitated by the disease. None was uremic. The body and tail of the pancreas from cadaveric donors was used, the grafts were revascularized to the recipient's iliac vessels. Six of the grafts provided control of blood glucose for 7–51 days. Five of the grafts then failed owing to rejection, and one had to be removed while still functioning, because of arterial bleeding. Important lessons have been learned concerning both surgical and immunological aspects of this form of treatment: 1) Ducto‐jejunostomy should be used to provide exocrine pancreatic drainage. 2) HLA‐DR typing for donor‐recipient selection and thoracic‐duct drainage as an adjunctive immunosuppressive measure should be used to reduce the incidence of graft rejection. 3) An elevation of the postprandial blood glucose concentration is a first sign of rejection and should cause treatment. 4) Graft rejection can be reversed by conventional steroid m

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1980.tb12865.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY