Use of the artificial B-cell (Biostator) in improving insulin therapy in unstable insulin-dependent diabetes.

The present study was designed to improve the conventional subcutaneous insulin treatment of labile insulin-dependent diabetic patients by means of the artificial B-cell (Biostator) during a combination of conventional treatment and a glucose-controlled insulin infusion. Eleven patients with no residual B-cell function and poor metabolic control were studied. All patients were treated as effectively as possible by conventional methods using a combination of regular and intermediate insulin under clinical conditions. In order to determine the inadequacy of previous insulin treatment, all patients were connected to the Biostator, and the profile of daily physical activity was simulated using a bicycle ergometer. Metabolic control was compared during a 6-day period before and after a 30-50-h connection to the artificial B-cell. Using a preselected blood glucose level of 80 mg/dl (4.44 mmol/L), the additional insulin requirement amounted to 45.5 +/- 11.1 U/24 h (N = 6). The day after connection to the artificial B-cell, the patients received a new insulin regimen according to the additional insulin delivery determined by the Biostator. No better metabolic control was achieved and frequent hypoglycemic episodes occurred in this group. Another group (N = 5) was therefore studied at a preselected blood glucose level of 130 mg/dl (7.22 mmol/L). The mean additional insulin delivery by the Biostator was lower (17.2 +/- 2.1 U/24 h; P less than 0.05) and all patients were significantly better equilibrated after the new insulin regimen derived from data given by the Biostator. The ratio of short-acting to intermediate-acting insulin was 3:1; 40% of the total dosage was given in the morning. This study demonstrates that using the Biostator in addition to subcutaneous insulin allows determination of the amount of additional regular insulin that should be administered to improve glycemic control in labile diabetes.

Reproducibility of insulin dosage on consecutive days of blood glucose control by an artificial beta-cell in brittle diabetic patients.

The profiles of blood glucose and of insulin dosage were compared between the first and second of 2 consecutive days of Biostator administration under constant conditions in 12 brittle type I diabetic inpatients. All blood glucose criteria and the daily insulin doses were reproducible between these 2 days for the entire group of patients. In nearly all patients, however, there were distinct but unsystematic differences between the 2 days in the diurnal patterns of insulin dose distribution. These differences could be ascribed to some stress reaction or inherent metabolic lability. It is concluded that, in these extremely labile diabetic patients, due to the insufficient short-term reproducibility of the outcome of an extracorporal artificial beta-cell, caution must be used when constant profiles are to be predicted from these doses for open-loop insulin delivery systems or for conventional subcutaneous injection therapy.

Mumps infection and insulin-dependent diabetes mellitus (IDDM).

In order to select a population at risk for the development of diabetes for a prospective study of the relationship of islet cell antibodies (ICA), islet cell surface antibodies ( ICSA ), and glucose tolerance after mumps infection, we carried out a screening program for diabetes. A diabetic survey was conducted among 1581 children (less than 16 yr of age) with mumps infection 14 mo before the survey, using a brief questionnaire combined with urinary glucose analysis. Responses to the screening program were obtained from 68.4% (N = 1080) of the children. Out of a total of 1080 subjects, 1069 (99%) had no diabetes mellitus, diabetic symptoms, or glucosuria. A "positive urine glucose screen" was obtained in 11 subjects (1%) of the study group. These individuals all had a normal oral glucose tolerance test according to the new WHO definition. A group of 86 children was randomly selected from the total group of 1080 children for follow-up glucose tolerance, ICA, and ICSA . Irrespective of the negative urine glucose screen impaired glucose tolerance was diagnosed in 3.5% (N = 3) of the 86 children. The prevalence of ICA and ICSA was 78% and 36%, respectively. The simultaneous prevalence of ICA and ICSA was 33%. The pathogenetic role of mumps infection and ICA/ ICSA and their possible relationship to slow progressive beta cell destruction remain to be elucidated.

The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone.

OBJECTIVE: To compare the therapeutic effects of the alpha-glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone. RESEARCH DESIGN AND METHODS: After a 4-week placebo run-in period, 201 patients in 18 centers in 4 countries were randomized in a double-blind manner to miglitol (50 mg t.i.d., followed by 100 mg t.i.d.), glibenclamide (3.5 mg q.d/b.i.d.), or placebo for 24 weeks. Efficacy criteria were changes from baseline of HbA1c, fasting and postprandial blood glucose and insulin levels, body weight, and serum triglycerides. RESULTS: Efficacy was assessed in 119 patients who completed the full protocol, and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis. Compared with placebo, mean baseline-adjusted HbA1c decreased by 0.75% (P = 0.0021) and 1.01% (P = 0.0001) in the miglitol and glibenclamide treatment groups, respectively. Blood glucose decreased slightly in the fasting state and considerably in the postprandial state in both treatment groups but not in the placebo group. Fasting insulin levels increased slightly (NS) in all treatment groups; however, postprandial insulin levels decreased with miglitol, while increasing markedly with glibenclamide (P = 0.0001 between all treatment groups). Gastrointestinal side effects (flatulence and diarrhea) occurred mostly in the miglitol-treated patients, while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia. CONCLUSIONS: Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.

Enhanced synthesis, storage, and secretion of insulin in pancreatic islets derived from obese subjects.

Insulin biosynthesis, content, and secretion were investigated in islets derived from pancreas specimens of normal weight (100.4 +/- 1.1% of ideal body weight) and obese (137.2 +/- 5.9% of ideal weight) patients. The pancreatic islets from the obese subjects were characterized by a significantly enhanced glucose-induced insulin secretion and biosynthesis and by an insulin content that was nearly double when compared with islets from the nonobese subjects. The results support the hypothesis that an enhanced beta-cell reactivity significantly contributes to the insulin hyperresponse observed in the obese state.

Computer-aided system for diabetes care in Berlin, G.D.R.

In the Centre of Diabetes and Metabolic Disorders of Berlin, G.D.R., a computer-aided care system has been used since 1974, aiming at relieving physicians and medical staff from routine tasks and rendering possible epidemiological research on an unselected diabetes population of a defined area. The basis of the system is the data bank on diabetics (DB), where at present data from approximately 55,000 patients are stored. DB is used as a diabetes register of Berlin. On the basis of standardised criteria of diagnosis and therapy of diabetes mellitus in our dispensary care system, DB facilitates representative epidemiological analyses of the diabetic population, e.g. prevalence, incidence, duration of diabetes, and modes of treatment. The availability of general data on the population or the selection of specified groups of patients serves the management of the care system. Also, it supports the computer-aided recall of type II diabetics, treated either with diet alone or with diet and oral drugs. In this way, the standardised evaluation of treatment strategies in large populations of diabetics is possible on the basis of uniform metabolic criteria (blood glucose plus urinary glucose). The system consists of a main computer in the data processing unit and of personal computers in the diabetes centre which can be used either individually or as terminals to the main computer. During 14 years of experience, the computer-aided out-patient care of type II diabetics has proved efficient in a big-city area with a large population.

[Trends in prescribing oral antidiabetic drugs. An analysis of the Berlin diabetes register covering 28 years]. / Trends in der Verordnung von oralen Antidiabetika. Eine Analyse des Berliner Diabetesregisters über 28 Jahre.

On the basis of the data collected by the (East) Berlin diabetes register, the prevalence of diabetes and trends in the prescription of oral antidiabetic agents over almost three decades were analysed. Between 1961 and 1989, the diabetic registration rate increased threefold, from 13,700 to 49,000. This corresponds to an increase in prevalence from 1.3% to 3.8%. At the beginning of the nineteen-sixties, only carbutamide and tolbutamide were prescribed, the respective percentages being 29% and 71%. From 1969 onward, the percentage of carbutamide decreased drastically and was no longer prescribed after 1973. With the introduction of the sulfonylureas ureas of second generation in 1969, the prescription of tolbutamide and glibenclamide showed an inverse evolution. In 1989, the prescription rate of tolbutamide was only 10% of all oral antidiabetics, while 88% of the patient group received glibenclamide. Since 1965, biguanides have been increasingly prescribed, reaching a peak of 32% of all prescriptions of oral diabetics by 1975. Thereafter, prescription of biguanides decreased. In 1979, biguanides accounted for only about 5% of all oral antidiabetics prescribed, and in 1989, for only 0.3%. The introduction of structured dietary teaching programs for type 2 diabetics resulted in a drastic change in the prescription of oral diabetics in the case of newly diagnosed patients: in 1968, primary management with oral antidiabetics peaked, accounting for 43.2% of the cases (newly diagnosed diabetics 3.049). This percentage decreased progressively and, in 1985, reached a figure of 17.5% in new cases of diabetes (total number of newly diagnosed cases 3.936). Since 1975, the percent of cases managed primarily with insulin has remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Incidence of severe hypoglycemia in relation to metabolic control and patient knowledge]. / Inzidenz schwerer Hypoglykämien in Abhängigkeit von der Stoffwechselqualität und dem Patientenwissen.

BACKGROUND: The question whether the incidence of severe episodes of hypoglycaemia in type I and type II diabetics correlates with the level of the patient's knowledge about hypoglycaemia and the quality of metabolic control. PATIENTS AND METHODS: A total of 234 consecutive type I diabetics (age and diabetes duration 48 and 16 years, respectively; blood glucose, self-monitored 63%) and 237 type II diabetics treated with glibenclamide (mean dose 6.7 mg/day) (age and diabetes duration 65 and 9 years, respectively; glucosuria, self-monitored 36%) who attended the Berlin outpatient diabetic centre were investigated. RESULTS: Of the type I diabetics 23 (9.8%) experienced a total of 32 severe episodes of hypoglycaemia (incidence 0.14 per patient/year). Patients at risk of experiencing hypoglycaemia were about 20 years younger, injected insulin more often (3.8 vs 2.3 injections/day; p < 0.01) and had a lower HbA1 level (7.8% vs 9.0%; p < 0.01) than those having no hypoglycaemic reactions. Ten of the 23 diabetics suffering severe episodes of hypoglycaemia showed signs of kidney disease. The most common causes of hypoglycaemia were dietary errors (18.7%) or incorrect doses of insulin (12.5%), alcohol consumption (12.5%) and unusual physical exertion (23%). In terms of their knowledge about hypoglycaemia, there were no notably differences between patients with and those without hypoglycaemic reactions. Among the 237 type II diabetics treated with glibenclamide, three (1.3%) experienced one episode of severe hypoglycaemia each (incidence: 0.013 patient/year). Old age, maximum dosage of glibenclamide (15 mg/day) and multimorbidity were characteristic of these patients. Enquiries showed that only 49% (n = 160) of all type II diabetes had adequate knowledge about hypoglycaemia. CONCLUSION: In type I diabetics, there appears to be no relationship between the hypoglycaemia risk and the patient's theoretical knowledge of hypoglycaemia. In future, apart from theoretical knowledge, more attention must be paid to practical training to improve awareness of hypoglycaemia. Educational programs for type II diabetics must attach more weight to the problem of hypoglycaemia.

[The "diabetic foot" syndrome. Association with other complications and the incidence of amputation]. / Das Syndrom des "diabetischen Fusses". Vergesellschaftung mit anderen Komplikationen sowie Inzidenz von Amputationen.

BACKGROUND: Only few studies have investigated the incidence of foot lesions and amputation rate in diabetic patients. PATIENTS AND METHOD: Thus, the 10-year incidence rates of first lower extremity amputation were studied in 560 diabetic patients, aged 35 to 55 years at baseline and followed up within the WHO-Multinational Study of Vascular Disease in Diabetes. Furthermore, we studied the frequency of other complications in 51 outpatients with "the diabetic foot syndrome". RESULT: In type 1 diabetic patients, the incidence rates (7.2/1,000 person-years for men and 7.6/1,000 person-years for women) were higher as compared with type 2 diabetic patients (4.1/1,000 and 4.3/1,000 per person-years for men and women, respectively). In multivariate analysis, duration of diabetes, hypertension, claudicatio intermittens, retinopathy and proteinuria emerged as potential risk factors. Outpatients with the "diabetic foot syndrome" were characterized by an advanced age and a long duration of diabetes (59 years and 22.5 years, respectively). 30 patients (58%) had type 1 diabetes and 21 (42%) had type 2, diabetes mellitus. The proportion of complications was as follows: foot lesions due to diabetic neuropathy or peripheral ischaemic vessel disease in 45.1% and 25.5%, and a combination of both in 29.4%. The majority of type 2 diabetic patients had lesions due to peripheral ischaemic vessel disease (77%); these patients were 10-years older as compared with patients with neuropathic lesions. Proliferative retinopathy was 4 times as high in patients with neuropathic lesions as compared with patients with ischaemic lesions (61% vs 15%). CONCLUSION: The findings once again emphasize the importance of education and training programs in elderly diabetic patients.

[Effect of fish oil concentrate on the lipoprotein profile of patients with type II diabetes mellitus]. / Zur Wirkung von Fischölkonzentrat auf das Lipoproteinprofil bei Patienten mit Diabetes mellitus Typ II.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased very-low-density lipoprotein (VLDL) and triglyceride concentrations as abnormalities of low-density lipoprotein (LDL) composition. Because fish oil has a strong triglyceride lowering effect in case of normolipemic subjects, we investigated the influence of supplementary fish oil diet in patients suffering from NIDDM (n = 19), who until now were not treated by drugs but only by diet. The study was started with a placebo-run-in-period for four weeks (phase I, 6 g rape seed oil capsules/d), followed by a verum period for twelve weeks (phase II, 6 g fish oil concentrate capsules/d), and a wash-out-period for four weeks (phase III, 6 g rape seed oil capsules/d). The fish oil supplementation contained at least 3 g eicosapentenoic and docosahexenoic acid. The lipoproteins, apolipoproteins, blood glucose, and insulin level (fasting and after load test) were checked at the beginning and at the end of each phase. In comparison to the placebo rape seed oil supplementation, the fish oil diet effected a decrease of serum triglycerides by 29%. LDL-cholesterol increased by 9%, HDL-cholesterol by 9% (especially HDL2-cholesterol), and apolipoprotein B by 4%. Apolipoprotein A-I was reduced by 9%. The fasting blood glucose and the glucose load test as the insulin level (fasting and after load test) showed no significant changes at the end of the verum period in comparison to the run-in-phase.(ABSTRACT TRUNCATED AT 250 WORDS)

[The psychological aspects of diabetics with the secondary failure of sulfonylurea therapy]. / Psychologische Aspekte bei Diabetikern mit Sekundärversagen einer Sulfonylharnstofftherapie.

Forty diabetics (19 men, 21 women; mean age 54 [41-66] years) with secondary failure of sulfonylurea treatment, were assessed by questionnaire (psychological-neurological state; scale of well-being; attitude towards achievement, and psychological aspects of performance), both before and four months after being put on insulin treatment, as to the way in which they experienced and dealt with the illness. Before the onset of insulin treatment, a general decrease in performance was the predominant symptom (29 patients), while only about half of the patients declared diabetes-specific symptoms. The necessity of insulin administration was experienced by 34 patients as a severe crisis in their chronic illness. Anxiety over failure in the act of injection (30 patients), as well as fear of the consequences regarding their job (25 patients) and of restriction in the personal sphere (31 patients) were the chief reasons for their dislike of insulin treatment. Four months after starting insulin treatment these anxieties had largely disappeared. The only remaining fear was that the necessity of insulin treatment meant that a serious stage of the disease had been reached (before insulin, 36; after insulin 18 patients). It is concluded that such patients should, as part of group therapy, become active participants in the instructions given to diabetics so that other patients can profit from their experience.

Does mumps infection play a role in the etiology and pathogenesis of insulin-dependent diabetes mellitus?

Numerous experimental findings in animals as well as epidemiological and clinical observations support the hypothesis that certain viruses play a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). Directly or via immune and/or autoimmune processes viruses might induce a beta-cell damage. An attempt is made to evaluate critically the arguments for the role of the mumps virus in the pathogenesis of IDDM. Based on their own experience, the authors hold the opinion that at present a causal connection between mumps infection and the development of IDDM cannot be proved beyond doubt. Prospective studies in humans including appropriate techniques of humoral and cellular immunity in relation to the beta-cell damage are required.

[Distribution spaces and catabolism of insulin]. / Verteilungsräume und Abbau von Insulin.

Exact knowledge of the distribution spaces and the loss rate of insulin is the prerequisite of the clinical use of an artificial B-cell. A critical review of the literary findings concerning these problems is performed and the still open problems are shown.

[Glucagon secretion in hyperlipoproteinemia and adiposity]. / Glukagonsekretion bei Hyperlipoproteinämie und Adipositas.

Summarizing the examinations demonstrate a normal A-cell-sensitiveness to glucose in patients with hyperlipoproteinaemia and normal glucose tolerance. Disturbances of the secretion of pancreatic glucagon are to be proved only in a common presence of a hyperlipoproteinaemia and diabetes mellitus and thus is rather characteristic for diabetes than for hyperlipoproteinaemia. From the bihormonal point of view (relation insulin-glucagon secretion) adipose persons with normal glucose tolerance after stimulation by glucose or amino acids are characterized by an anabolic state, which theoretically means an increase and/or persistence of the fat depot.

[Effect of insulin on stimulated lipolysis in obesity with normal carbohydrate tolerance and unimpaired thyroid function]. / Untersuchungen zur Insulinwirkung auf die stimulierte Lipolyse bei Adipositas mit normaler Kohlenhydrattoleranz und ungestörter Schilddrüsenfunktion.

The effect of intravenous injection of 0.1 I.U./kg insulin on blood glucose response and on lipolysis, induced by intravenous infusion of 0.2 microgram/kg - min norepinephrine, were studied in 12 normal subjects and 17 obese patients with normal 50 g oral glucose tolerance test and normal thyroid function. In the obese group the insulin-induced hypoglycemia during norepinephrine-infusion was significantly less than in normal subjects. Moreover, the inhibition of norepinephrine-stimulated FFA and glycerol-release by insulin was significantly less in obesity as compared with the non-obese group. It is concluded that in obesity the action of insulin is decreased both in carbohydrate metabolism and in lipolysis. These results provide arguments for the role of an impaired antilipolytic insulin effect in the pathogenesis of hyperinsulinism in obesity.