Continuous monitoring of blood sugar in brittle diabetics

Summary The blood glucose was measured continuously for periods of up to twenty-nine hours in five patients. The method, which does not require heparinization of the patient, is described. — Three unstable diabetics were investigated. In two, diabetic control was considerably improved as a result of alterations made to their therapeutic regime following this investigation. The symptoms of the third diabetic patient were due to complications of diabetes rather than to the disease itself. — The results in these three patients are contrasted with those obtained in two acromegalics (one of whom was also diabetic). Attention is drawn to the occurrence of fasting hyperglycaemia in the early hours of the morning in the brittle diabetics and to the rapidity with which the blood glucose rises. It is thought that growth hormone is not directly responsible for this hyperglycaemia, since marked insulin sensitivity is maintained.

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Dauermessung der Blutzuckerspiegel bei labilen Diabetikern

Zusammenfassung Bei 5 Patienten wurden die Blutzuckerspiegel fortlaufend über Zeiträume von bis zu 29 Std. bestimmt. Die Methodik, die keine Heparinisierung des Patienten erforderlich macht, wird beschrieben. Drei nicht stabile Diabetiker wurden untersucht. Bei zwei Patienten besserte sich die Diabetes-Einstellung beträchtlich auf Grund von Änderungen in der Therapie, die auf Grund dieser Untersuchungsergebnisse vorgenommen wurden. Die Symptome des dritten Diabetikers waren in erster Linie auf Diabeteskomplikationen und nicht so sehr auf die Krankheit selbst zurückzuführen. Die Ergebnisse bei diesen drei Patienten werden mit denen von 2 Akromegalen verglichen, von denen einer ebenfalls einen Diabetes aufwies. Es wird besonders auf das Vorkommen einer Nüchtern-Hyperglykämie in den frühen Morgenstunden bei labilen Diabetikern und auf die Geschwindigkeit des Blutzuckeranstieges hingewiesen. Es wird angenommen, daß das Wachstumshormon nicht direkt für diesen Blutzuckeranstieg verantwortlich ist, da die Insulinempfindlichkeit erhalten bleibt.

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Contrôle continu de la glycémie chez des diabétiques instables

Résumé La glycémie a été mesurée continuellement pendant des périodes allant jusqu'à 29 h chez 5 malades. On décrit la méthode qui n'exige pas l'héparinisation du malade.— Trois diabétiques instables ont été étudiés. Chez deux d'entre eux l'équilibre diabétique a été considérablement amélioré par suite des modifications apportées à leur régime thérapeutique qui a suivi cette investigation. Les symptômes du troisième diabétique étaient dus à des complications du diabète plutôt qu'au diabète lui-même. — Les résultats chez ces trois patients sont comparés avec ceux obtenus chez deux acromégales (dont l'un était aussi diabétique). On attire l'attention sur l'apparition de l'hyperglycémie à jeun dans les premières heures de la matinée chez les diabétiques instables et sur la rapidité avec laquelle la glycémie s'élève. On pense que l'hormone de croissance n'est pas directement responsable de cette hyperglycémie, puisqu'une sensibilité marquée à l'insuline est maintenue.

     

Causes of death in Japanese patients with diabetes based on the results of a survey of 45,708 cases during 2001–2010: Report of the Committee on Causes of Death in Diabetes Mellitus

The principal causes of death among 45,708 patients with diabetes (29,801 men and 15,907 women) who died in 241 hospitals throughout Japan during 2001–2010 were determined based on a survey of the hospital records. Autopsy had been conducted in 978 of the 45,708 cases. The most frequent cause of death was malignant neoplasia (38.3%), followed by, in order of descending frequency: infections (17.0%); and then vascular diseases (14.9%), including renal failure (3.5%), ischemic heart diseases (4.8%) and cerebrovascular diseases (6.6%). Diabetic coma associated with hyperglycemia with or without ketoacidosis accounted for only 0.6% of the deaths. In regard to the relationship between the age and cause of death in patients with diabetes, the incidence of death due to vascular diseases was higher in patients over the age of 30 or 40 years, and the 97.0% of the total death due to vascular diseases was observed in patients over the age of 50 years. The incidence of death due to infectious diseases, especially pneumonia, increased in an age‐dependent fashion, and the 80.7% of the total death due to pneumonia was observed in patients over the age of 70 years. ’Poorer’ glycemic control was associated with the reduced lifespan of patients with diabetes, especially of those with nephropathy. The average age at death in the survey population was 72.6 years. The lifespan was 1.6 years shorter in patients with ‘poorer’ glycemic control than in those with ‘better’ glycemic control. In patients with diabetes of less than 10 years’ duration, the incidence of death due to macroangiopathy was higher than that due to nephropathy. Of the 45,708 patients with diabetes, 33.9% were on oral medication, 41.9% received insulin therapy and 18.8% were treated by diet alone. Among the patients in whom the cause of death was diabetic nephropathy, a high percentage, 53.7%, was on insulin therapy. The average age at death of the 45,708 patients with diabetes was 71.4 years in men and 75.1 years in women. However, the report of the Ministry of Health and Welfare of Japan in 2010 set the average lifespan of the Japanese at 79.6 years for men and 86.3 years for women. Thus, the average lifespan of patients with diabetes still appears to be shorter than that of the general population in Japan. However, the differences in lifespan between patients with diabetes and the general population were shorter than those in the former surveys.     

The effects of soybean isoflavones and 17β-estradiol in uterus and mammary glands of diabetic rat models

The objective of this study was to evaluate the action of soy isoflavones and 17 beta estradiol on the extracellular matrix in the uterus and mammary gland of diabetic rats. Sixty adult female rats underwent ovariectomy, then randomized into seven groups of ten animals each: Non-diabetic: GI Sham control animals ovariectomized; and GII control ovariectomized that received propylene glycol vehicle. Diabetic: GIII Sham control diabetic animals ovariectomized; GIV ovariectomized diabetic animals receiving propylene glycol vehicle; GV diabetic ovariectomized animals treated with soy isoflavones (150?mg/kg by gavage); GVI ovariectomized diabetic rats treated with estrogen (17b-estradiol, 10?mg/kg, subcutaneously); GVII diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage), and with estrogen (17b-estradiol, 10 mg/kg combination therapy). Treatments occurred during 30 consecutive days. After animals euthanasia, a portion of the uterus was immersed in liquid nitrogen for molecular biology analysis, the other portion of uterus and mammary glands were removed and processed for paraffin embedding. Soy isoflavones (GV) and 17b estradiol improved the production of compounds of extracellular matrix, such as small leucine-rich proteoglycans (SLRPs). The combination of both therapies had an additive effect in SLRPs expression. Soy isoflavones contribute to the uterine integrity of SLRPs of diabetic rats.     

Increased killer cell activity in insulin dependent (Type 1) diabetes mellitus

Summary Antibody dependent cell mediated cytotoxicity in relation to the levels of circulating killer cells was investigated in 16 newly diagnosed classical insulin dependent (Type 1) diabetics, 11 islet cell antibody positive non diabetic children with at least one HLA haplotype in common with their diabetic sibling, and in 15 normal controls. Antibody dependent cell mediated cytotoxicity was evaluated using, as target, ⁵¹Cr labelled human 0⁺ erythrocytes sensitised with an anti-CD antiserum. Killer cells were measured by the low affinity E-rosetting cell technique. Increased killer cell levels (>normal mean + 2SD) were accompanied by a significant enhancement in antibody dependent cell mediated cytotoxicity both in newly diagnosed diabetics (p < 0.05) and in unaffected siblings (p < 0.01). These preliminary results indicate that raised antibody dependent cell mediated cytotoxicity is a feature of insulin dependent diabetes at diagnosis and suggest that active B cell damage might be occurring some time before the onset of clinical symptoms.     

糖尿病视网膜病变与糖化血红蛋白的关系

目的探讨糖化血红蛋白(glycated hemoglobin,HbA1c)与2型糖尿病性视网膜病变(diabetic retinopathy,DR)的关系。方法 300例2型糖尿病患者,根据其有无糖尿病视网膜病变及病变程度分为3组:正常视网膜组(non-diabetic retinopathy group,NDR)、非增殖型视网膜病变组(nonproliferative diabetic retinopathy group,NPDR)和增殖型视网膜病变组(proliferative diabeticretinopathy group,PDR),同时测定患者HbAlc浓度,并对相关因素如年龄、性别、病程、血压、糖尿病家族史等进行统计分析。结果 NDR组、NPDR组和PDR组的HbA1c浓度差异有统计学意义(P<0.05)。结论 HbA1c可作为监测DR发生和发展的重要指标之一。     

Islet and beta cell volumes in offspring of severely diabetic (ketotic) chinese hamsters

Summary Chinese hamsters bred at the Upjohn Laboratory were studied at varying ages from 15 days to 19 months. Diabetic animals three to six months and those 10 to 19 months of age were glycosuric and hyper glycemic; there was ketonuria and ketonemia but blood glycerol and fasting plasma insulin levels were low when these values were compared with normal control animals of comparable ages. Using quantitative technics developed in our laboratory, the volumes of islets, beta cells and beta granules were diminished. The increase in volume of nongranular cells is progressive with duration of diabetes. Glycogen infiltration was observed in beta cells of these diabetic animals. — Although offspring (fifteen-day-old weanlings) of the mating of two severely diabetic (ketotic) animals were normoglycemic and glycosurie, their plasma insulin levels were higher than those of their controls. The islet volume was somewhat higher than that of the controls but the beta cells were degranulated both by light and electron microscopy; the beta cells exhibited glycogen infiltration. These results are consistent with the thesis that the primary defect is in insulin biosynthesis.

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Insel- und B-Zell-Volumen im Pankreas von Nachkommen schwer diabetischer chinesischer Hamster

Zusammenfassung Mit von den Autoren entwickelten morphometrischen Methoden wurde das B-Zell-Volumen im Pankreas chinesischer Hamster der Upjohn Kolonie bestimmt. Das Alter der untersuchten Tiere schwankte zwischen 15 Tagen und 19 Monaten. Die diabetischen Tiere waren entweder 3 – 6 oder 10–19 Monate alt. Sie waren hyperglykämisch und glykosurisch, teilweise bestand Ketonurie. Die Plasmainsulin- und Glyzerin-Konzentrationen im Gesamtblut waren niedriger als diejenigen gleichaltriger Normaltieren erniedrigt. Bei diabetisehen Tieren waren B-Zell- und-Granula-Volumen vermindert. Mit zunehmender Dauer des Diabetes nahm der Anteil der nicht granulierten B-Zellen zu. Die B-Zellen diabetischer Tiere zeigten Glykogeninfiltration. 15 Tage alte Nachkommen zweier ketotisch-diabetischer Eltern waren normoglykämisch, hatten aber im Vergleich zu gleichaltrigen Kontrolltieren erhöhte Plasmainsulin-Konzentrationen. Das Inselzellvolumen war gegenüber der Norm erhöht, aber die B-Zellen waren degranuliert und zeigten Glykogeninfiltration. Diese Resultate stimmen mit der Hypothese überein, daß der primäre Defekt, der beim chinesischen Hamster die Entwicklung eines diabetischen Syndroms zur Folge hat, die Biosynthese des Insulins betrifft.

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Le, volume des îlots de Langerhans et des cellules B du pancréas de la progéniture de hamsters chinois sévèrement diabetiques

Résumé Des hamsters chinois provenant de la colonie des Laboratoires Upjohn ont été étudiés à différents âges allant de 15 jours à 19 mois. On trouve une glycosurie et une hyperglycémie chez les animaux diabétiques de 3 à 6 mois et chez ceux de 10 à 19 mois. On observe également une cétonurie et une cétonémie, mais les taux de glycérol sanguin et les taux d'insuline plasmatique à jeun sont bas par comparaison à ceux détectés chez des témoins d'âge comparable. Le volume des îlots, des cellules et des granules, mesuré par des méthodes quantitatives élaborées dans notre laboratoire, est diminué. Le volume des cellules non-granulées augmente progressivement avec la durée du diabète. On observe une infiltration de glycogène dans les cellules B des animaux diabétiques. Bien que la progéniture, âgée de 15 jours, de deux animaux sévèrement diabétiques (avec cétose) ait des taux normaux de glycémie et une glycosurie, leur insulinémie est plus élevée que celle mesurée chez les témoins. Le volume de leurs îlots est un peu plus grand que celui des contrôles, mais, en microscopie optique et électronique, les cellules sont dégranulées et montrent une infiltration de glycogène. Ces résultats confirment l'hypothèse que le défaut primaire est au niveau de la biosynthèse de l'insuline.

     

Limited joint mobility (LJM) in elderly subjects with type II diabetes mellitus

LJM is frequently observed in young subjects with insulin-dependent diabetes mellitus (IDDM). Aim of this study was to evaluate whether non-insulin-dependent diabetes mellitus (NIDDM) increases the risk of LJM in elderly subjects. Thirty patients (15 males, 15 females, mean age 73.93 ± 12.72 years) with NIDDM in good glycemic control were compared with thirty non-diabetic elderly, well matched for sex and age (15 males, 15 females, mean age 74.3 ± 4.24 years), and with ten young normal subjects (5 males, 5 females, mean age 26.3 ± 1.56 years). In these subjects, the range of motion (ROM) of ankle, knee, hip, elbow and shoulder were measured with a double-armed goniometer. Moreover, abnormalities of supraspinatus, patellar and Achilles tendons were evaluated with a standardized ultrasound (US) procedure. A significant reduction in the mobility of all joints was found in elderly subjects, compared to younger ones, with exception for the knee and elbow flexion. Elderly patients with diabetes, compared with their age-matched counterpart, showed LJM for ankle dorso- and plantar flexion, hip flexion and adduction, shoulder abduction and flexion. Moreover, tendons sonographic abnormalities were more frequently observed in diabetics. Our data confirm that diabetes worsens the LJM in the elderly, increasing the cross-linking of collagen by the non-enzymatic advanced glycation end products formation.     

Determination of total serum insulin (IRI) in insulin-treated diabetic patients

Summary A routine method is described for the determination of total IRI (imraunoreactive insulin) in insulintreated diabetics. The method involves an easy acid ethanol extraction, whereby antibody-bound IRI is dissociated and separated, together with the free IRI from the serum proteins and the antibodies. The recovery of IRI in this procedure is about 80%. After the separation, the isolated total IRI is measured in an immunoassay, using ethanol for the separation of free and antibody bound¹²⁵I-insulin. In 169 diabetic patients treated with insulin in doses of from 6 to 120 units/day, the fasting serum total IRI was between 6 and 4374 U/ml, with a mean of 392 U/ml. During treatment with insulin, the level of total IRI increased from normal values, registered during the first two months, to a higher level which became stable after about 5 months of treatment. The increase in IRI occurred simultaneously with the formation of antibodies. Insulin-resistant patients showed very high IRI levels.

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Bestimmung des Gesamtserum-Insulins (IRI) bei insulinbehandelten Diabetikern

Zusammenfassung Für die Bestimmung des Gesamt-IRI (immunoreaktiven Insulins) bei Diabetikern, die mit Insulin behandelt wurden, wird eine Routinemethode beschrieben. Die Methode schließt eine einfache SäureÄthanol-Extraktion ein, wobei das antikörpergebundene IRI dissoziiert und zusammen mit dem freien IRI von den Serumproteinen, einschließlich den Antikörpern, getrennt wird. Bei diesem Verfahren werden etwa 80% des IRI wiedergefunden. Nach der Trennung wird das isolierte Gesamt-IRI immunologisch gemessen. Für die Trennung des freien von dem an Antikörper gebundenen¹²⁵I-Insulin wird Äthanol verwendet. Bei 169 Diabetikern, die mit 6 bis 120 E Insulin/Tag behandelt wurden, lag das Nuchternserum-Gesamt-IRI zwischen 6 und 4374 E/ml (Mittelwert 392 E/ml). Im Laufe der Insulinbehandlung stieg das Gesamt-IRI von Normalwerten, die während der ersten 2 Monate registriert wurden, auf ein höheres Niveau an, das sich nach etwa 5 Monaten Behandlungsdauer stabilisierte. Der Anstieg des IRI erfolgte gleichzeitig mit der Bildung von Antikörpern. Bei insulinresistenten Patienten ergaben sich sehr hohe IRI-Konzentrationen.

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Determination de l'insuline totale chez les diabétiques traités a l'insuline

Résumé On décrit une méthode de routine pour le dosage de l'IRI (insuline immunoréactive) totale chez les diabétiques traités par l'insuline. La méthode comprend une extraction à l'acide-éthanol, très simple, pendant laquelle l'IRI liée aux anticorps est dissociée et séparée ainsi que l'IRI »libre« des protéines sériques, anticorps compris. La récupération de l'IRI par cette méthode est aux environs de 80%. Après la séparation, l'IRI totale isolée est mesurée par un dosage immunologique qui se sert de l'éthanol afin de séparer l'I¹²⁵-insuline libre de celle liée aux anticorps. Chez 169 malades diabétiques traités par l'insuline à des doses allant de 6 à 120 unités par jour, l'IRI totale sérique à jeun était de 6 à 4374 U/ml, avec une moyenne de 392 U/ml. Pendant le traitement par l'insuline le taux de l'IRI totale est passé des niveaux normaux, enregistrés pendant les deux premiers mois, à des niveaux plus éleévs qui se stabilisent 5 mois environ apres le début du traitement. L'augmentation de l'IRI coïncide avec la formation d'anticorps. Les malades insulino-résistants présentent des valeurs très hautes d'IRI.

     

Controlled extension of oral antidiabetic therapy on former insulin dependent diabetics by means of the combined i.v. glibenclamide-glucose-response-test

Summary A new sulphonylurea response test is described for predicting the results of long-term treatment with a recently developed sulphonylurea compound, glibenclamide, particularly in insulin-dependent tolbutamide-non-responsive elderly diabetics. The test is based on the observation that the insulin-stimulating capacity of glucose and the determination of the insulin increases are strikingly potentiated following glibenclamide plus glucose i.v. (25 plus 0.33 g/kg body weight) in serum samples where insulin binding antibodies have been removed. 11 out of 40 diabetics demonstrating between 60 and 90 min following injection, a mean increase of insulin of more than 500 per cent above the initial values, correlated satisfactorily with successful long-term oral treatment with glibenclamide. A positive glibenclamide-glucose-response test contrasted with primary failure of glibenclamide therapy in only one patient suffering from haemochromatosis. Oral treatment with glibenclamide may have certain advantages over insulin therapy, especially in elderly diabetics suffering from visual impairment, who are unable to inject themselves with insulin.Support of this Study by Deutsche Forschungsge-meinschaft (Pf 38/28) is gratefully acknowledged.