[Long-term effect of combination glibenclamide-insulin treatment in the secondary failure of sulfonylurea therapy--results of a one-year double blind study]. / Langzeiteffekt der Glibenclamid-Insulin-Kombinationsbehandlung beim Sekundärversagen der Sulfonylharnstofftherapie--Ergebnisse einer einjährigen Doppelblindstudie.

The long-term efficacy of combined insulin-glibenclamide treatment was investigated in 79 secondary drug failure patients by means of a double-blind, randomized placebo-controlled study. During a one-year follow-up period the patients on insulin plus glibenclamide required significantly lower exogenous insulin doses. Coincidentally, C-peptide concentrations were significantly raised in the verum versus the placebo group. Additionally, the administration of glibenclamide resulted in a decreased level of hyperglycaemia during the first six months of the observation period. Glibenclamide withdrawal after six and again after twelve months of the combined therapy provoked a deterioration of glycaemic control, as well as a lowering of the C-peptide concentrations. The findings demonstrate a prolonged beneficial effect of the combined treatment, in contrast to the solely short-term effects predicted by numerous studies. The metabolic improvement must be ascribed in part to the beta-cytotropic effect of glibenclamide. Extrapancreatic pathways via receptor/postreceptor mechanisms cannot be excluded.

Long-term diabetes--associated factors in survivorship and mortality.

Patients with long standing diabetes mellitus were analysed in order to identify associated factors in survivorship and mortality. Two population-based investigations were performed. In the Erfurt district all 20 years' survivors (208 patients, survival time up to 42 years) were studied longitudinally. Within the total diabetic population of the GDR all 40 years' survivors (159 patients, survival time up to 59 years) were investigated cross-sectionally in a multicentre study. During a 12-year follow-up a 2,6 fold excess mortality was registered. Although most patients in both studies were insulin-treated type-1 diabetics, death due to renal failure was observed only in 7%. In general the appearance of macroangiopathy was considerably postponed. Coronary heart disease represented the main cause of death (41.9%). Taking together both studies, to successfully overcome several decades of diabetes appears to be associated with age, age of onset, body weight, blood pressure, daily insulin dose, serum triglycerides, dietetic adherence and degree of compliance. In long-term diabetics, duration of illness exerts no prognostic influence. Some patients have survived for even half a century of diabetes despite additional atherogenic risk factors and bad compliance. Obviously, long-term diabetes is a multifactorial event including protective mechanisms yet unknown. Most long-term studies in diabetes so for have been based on case material from specialized centres (Oakley et al. 1974, Paz-Guevara et al. 1975, Dekkert et al. 1975) or have been performed without an epidemiologic background (Chazan et al. 1970, Ryan et al. 1970, Cochran et al. 1979). Due to unavoidable selection factors those studies do not provide representative samples of the diabetic population.(ABSTRACT TRUNCATED AT 250 WORDS)

[Proliferative retinopathies in diabetes mellitus--cross sectional study in the Erfurd city and rural district]. / Proliferative Retinopathien beim Diabetes mellitus--Querschnittsuntersuchung im Stadt- und Landkreis Erfurt.

Among the 9,173 diabetics of the city and the district of Erfurt (4.3% of the population) 37 patients with a proliferative retinopathy (0.4% of all diabetics) were found. The impairment of vision was very different: 9 patients had still a full vision, 7 patients were completely blind and only able for light perception, respectively. On the group average the 3rd degree retinopathy developed after 19 years of diabetes. In comparison to the type 1 diabetics (n = 17) the type 2 diabetics (n = 15) showed the more progressing courses. The period from the appearance of the first ophthalmologically provable retinal changes (R I) up to R III was in these cases about 5 years shorter than in the type 1 diabetics. The cause for the proliferative retinopathy is multifactorial. Our results plead for the fact that among the risk factors for the retinal microangiopathy apart from the duration of the disease the quality of metabolism and the arterial hypertension are decisive determinants both in type 1 and in type 2 diabetics. In order to avoid and to delay, respectively, severe impairments of vision, from the beginning of diabetes metabolism and blood pressure should be stabilized as well as possible and by means of regular short-term ophthalmoscopic controls well-timed light and laser coagulations should be striven for.

[Prospective follow-up studies in long-term diabetes. Results of the Erfurt study]. / Prospektive Verlaufsbeobachtungen beim Langzeitdiabetes. Ergebnisse der Erfurt-Studie.

In 1970, in cooperation with the 14 district diabetic consultation centers of the Erfurt region (German Democratic Republic), all 208 known diabetics of the region with a known history of diabetes of at least 20 years (maximally 42 years) were registered and underwent multidisciplinary investigations. They were followed prospectively for at least 15 years. At the end of this period of observation, in 1985, 135 patients had died, 59 were still alive, the course of 14 is unknown. Of the 59 patients who were still alive in 1985, 49 (44 type I) were re-examined. There was a 2.1 times excess mortality rate compared with metabolically normal, interindividually paired (by age, sex and weight) controls. Cause of death in 89 patients (69.9%) was arteriosclerosis, predominantly of the coronaries, renal failure in only 9 (6.7%). Nearly all those patients who already in 1970 had evidence of advanced microangiopathies (proliferating retinopathy; persistent proteinuria) and/or macroangiopathy (authors' scoring system for coronary, cerebral and peripheral vascular disease) died during the observation period. Ophthalmoscopically normal or only mildly abnormal fundi revealed little tendency towards progression, despite the 35-55 years' duration of diabetes. Similar observations were made in the survivors as regards initially normal ECGs. The prognosis of long-term diabetes was decisively influenced by age and the severity of any arteriosclerotic disease, but not by the duration of diabetes.

[Tumour frequency in autopsy cases. VI. Hodgkin's disease (author's transl)]. / Die Häufigkeit der Tumoren im Obduktionsgut. VI Mitteilung: Die Lymphogranulomatose

The analysis is based on the catalogue of neoplasms notifiable in the German Democratic Republic (ICD-Code Nrs. 140-209, 210.2, 211.3, 211.9, 225, 226.2, 226.3, 253.0, 253.2, 702, 757.2). At the Medical Academy of Erfurt 22155 autopsies (12212 males, 9943 females) of adults (15 years and upwards) were registrated in the period from 1950 to 1966. 128 cases of Hodgkin's disease (0.6% of autopsies and 1.7% of malignant tumours) were observed among them. The cases are distributed among 80 males (0.7% of males) and 48 females (0.5% of females). There is no difference in frequency. Age and sex distribution, frequency and localization of lymph node and organ involvement are presented.

[Studies of nephropathies in 168 diabetic patients with over 20-year onset of the disease]. / Beobachtungen zur Nephropathie bei 168 Diabetiken mit über 20jähriger Krankheitsdauer

Within a clinical epidemiological investigation 168 diabetics were examined multidisciplinarily who survived the beginning of their disease by at least 20 years. The qualitative proof of protein in the urine was regarded as criterion for the presence of a diabetic nephropathy. 29% of the long-term diabetics showed a proteinuria. In a control group of probands with healthy metabolism, however, only 2.5% proteinurias were found. Statistically ascertained correlations were the results in cases of proteinuria and retinopathy (microangio-pathy). Particularly close were the relations of proteinuria to arteriolosclerosis (macroangiopathy). There were no relations between the proof of a proteinuria and the quality of the control of the carbohydrate metabolism which was pursued during decades.

[Electrocardiographic findings in a selection-free number of cases of long-term diabetic patients]. / Elektrokardiographische Befunde bei einem selektionsfreien Krankengut von Langzeitdiabetikern

When the conventional ECG after resting was used for establishing frequency and degree of severity of the ischaemic heart disease the stronger cardiac endangering of the longterm diabetic could be ascertained only from residues of an infarction (pathologic Q- and QS-types). With regard to all electrocardiographic criteria of the ischaemic heart disease according to the WHO-definition concerning the coronary risk a dependence on age, over-weight and increase of blood pressure was found without essential differences between the two groups. According to data in literature ischaemic reactions in diabetics are significantly more frequently to be expected only by inclusion of the electrocardiogram after work. Among the group of diabetics the frequency of the ischaemic heart disease increased with the duration of the disease. In contrast to retinopathy there was no dependence on the quality of the metabolic condition.

[Development of angiopathies in type 2 diabetes mellitus--results of a prospective 10 year study]. / Angiopathieentwicklung beim Typ 2-Diabetes mellitus--Ergebnisse einer prospektiven 10-Jahres-Studie.

In 150 newly detected type 2 diabetics the formation of macro- and microangiopathic complications during a 10-year control period was prospectively analysed, in order to demarcate possible factors of influence for the vascular prognosis under preventive points of view. Already at the time of manifestation there was with 34.3% an above average high prevalence of the coronary heart disease, particularly in the female sex. The prevalence of the coronary heart disease further increased to 49.7% in the course of diabetes and showed a correlation to the initial age, to the existence of overweight, hypertension, hyperlipoproteinaemia and nicotine consumption. The PMA was found comparatively more infrequent in the manifestation of diabetes (9.7%), but in the course of the disease highly significantly and independently of sex increased to 61.9%. The development of PMA was correlated with the age, the existence of hypertension and overweight. The frequency of retinopathy increased from initially 3.7% to 18.7%, the prevalence of nephropathy from 4.0% to 22.2%, without having found prognostic influence factors at the date of the diagnosis of diabetes.

Association of coronary heart disease with serum lipid and apolipoprotein concentrations in long-term diabetes. Results of the Erfurt study.

The Erfurt study is concerned with the follow-up of all the 208 long-term diabetics out of the closed area of the Erfurt district with an at least 20 years' diabetes survival in 1970. In 1980 risk factors for coronary heart disease (CHD) were assessed in 71 (85% type I diabetes) out of 76 patients still alive. Progression of CHD within the subsequent five years (death due to CHD in 8 cases and progression of the ECG findings according to the Minnesota code in 3 cases) was associated with older age, lower body mass index, higher triglycerides, and a higher total cholesterol/HDL cholesterol ratio in comparison with the surviving patients without progression (n = 41). No significant differences could be found with regard to sex distribution, age at diabetes onset, duration of diabetes, percentage of type I diabetes, systolic and diastolic blood pressure, smoking behavior, prevalence of nephropathy, glycemic control, and serum levels of total cholesterol, LDL cholesterol, and HDL cholesterol. The subsequent reinvestigation in 1985 also included the determination of apolipoproteins. Since type II diabetes was not equally distributed, only type I diabetics were considered for the comparison of patients with ECG findings suggestive of CHD (n = 5) with the remaining subjects (n = 35). In addition to the above mentioned differences, CHD in long-term type I diabetes was also accompanied by lower HDL cholesterol, lower apolipoprotein A-I, and a higher apolipoprotein B/apolipoprotein A-I ratio. Substantially similar differences could be observed when type II diabetics were not excluded (10 patients with and 37 patients without CHD). It is concluded that the lipoprotein pattern is important for the survival in long-term diabetes.

[Results of a multicentric study on long term diabetes in the East German population]. / Ergebnisse einer multizentrischen Studie über den Langzeitdiabetes in der DDR-Population.

In the diabetes population of the GDR by means of the dispensary network of the consulting points 159 diabetics with a duration of the disease of at least 40 years were recognized and investigated on the basis of a standardized documentation material. 23 diabetics had survived their disease for longer than 50 years. The number of benign long-term courses in males was absolutely and relatively higher. The following frequencies of normal findings were stated: 55 per cent good general condition, 78 per cent normal weight/or underweight, 33 per cent no retinopathy, 65 per cent no proteinuria, 49 per cent normal ECG in rest. A proliferating retinopathy was found in 10 per cent, creatinine increases in 10 per cent, coronary infarctions in 32 per cent, gangrene and amputations, respectively, in 9 per cent. There was no striking longevity of the parents. In the majority of cases disciplined patients with a well-balanced metabolic condition were concerned. The partly existing atherogenic factors of risk (hypertension, smoking habits) speak for complex causes of the favourable course, including vasoprotective factors up to now not yet clarified.

[Frequency of lipid metabolism disorders in blood donors]. / Untersuchungen zur Haüfigkeit von Fettstoffwechselstörungen bei Blutspendern.

It is reported on a screening test examination for disturbances of the lipometabolism in 3,714 blood donors by means of the estimation of the beta-lipoproteins. In 240 blood donors (6.5%) increased values of beta-lipoproteins were found. 45 donors with values increased for several times underwent an after-examination by a specialist, by means of which among others in eight of them an asymptomatic diabetes mellitus was found. The estimation of the beta-lipoproteins as screening test examination is ingenious and serves the improved cure for the health of the donors.

Serum lipids and apolipoproteins in relation to glycaemic control and diabetic nephropathy in long-term survivors of diabetes: results of the Erfurt Study.

Follow-up data of all 208 long-term diabetics (duration of the disease at least 20 years) living in the closed area of the Erfurt district in 1970 had demonstrated the importance of lipoprotein pattern for longevity. Now the dependence of lipoprotein levels on both the diabetes-related conditions nephropathy and glycaemic control has been examined in 47 of them, still alive in 1985 that means 35 or more years after the onset of diabetes. Glycaemic control was assessed by measuring the glycosylated haemoglobin (n = 44). Diabetic nephropathy was assumed in case of persistent proteinuria. Poor glycaemic control (n = 16) was associated with increased levels of atherogenic lipoproteins as reflected by higher concentrations of total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides, as well as a changed HDL composition indicated by a decreased HDL cholesterol/apolipoprotein A--I ratio. Higher ratios of total cholesterol to HDL cholesterol and apolipoprotein B to apolipoprotein A--I point to an increased risk of developing atherosclerotic diseases in poorly controlled diabetics. 86% of the well controlled long-term diabetics had non-pathological values of LDL cholesterol, triglycerides, apolipoprotein B, HDL cholesterol, and apolipoprotein A--I but only 31% of the poorly controlled patients did so. Diabetic nephropathy in the absence of chronic renal failure (n = 10) was characterized by higher values of LDL cholesterol, triglycerides, total cholesterol/HDL cholesterol, and apolipoprotein B/apolipoprotein A--I. 80% of the subjects with a pathological lipoprotein pattern were proteinuric or in poor glycaemic control or both. Therefore, it is concluded that prevention of these two conditions might help to delay atherosclerosis via its beneficial influence on lipoprotein metabolism.

[Comparative analysis of electrocardiographic findings in diabetics and metabolically healthy persons]. / Vergleichende Analysen elektrokardiographischer Befunde bei Diabetikern und Stoffwechselgesunden

The electrocardiograms of 447 diabetics and of the same number of non-diabetic test persons who were coordinated as biostatic twins, taking into consideration age, sex, and weight, were evaluated according to the Minnesota-code and compared. The cardiac endangering of the diabetics was most clearly expressed in the larger frequency of infarctions and the chronic-ischaemic heart disease which can be proved in all age groups. Diabetic males with short duration of diabetes showed the highest frequency of infarctions. The frequency of coronaropathy which is not increased in most age groups in the long-term diabetics compared with the control persons characterizes them as a positive selection of diabetics with an apparantly primarily low atherogenic potency. Hypertonus and/or adiposity were concomitant with a nearly doubled frequency of the ischaemic heart disease. The breadth of the P-wave as a possible reference to angiopathic changes in the region of the atrium was significantly larger in the diabetics in all age groups than in the control group.

[Intensified therapy of newly detected maturity onset diabetes]. / Ergebnisse einer Intensivierung der Therapie des neuentdeckten Maturity onset-Diabetes.

In a prospective study 150 newly detected maturity onset-diabetics were randomized in 2 biostatistically comparable groups and underwent a treatment of different intensity. While the patients of the control group were treated according to the routine method used up to now in the dispensary for diabetics, in the intervention group an intensifying of the therapy took place, taking particular into consideration the body weight as well as the carbohydrate and fat metabolism. The decrease of body weight achieved by dietary intensive care proved to be the decisive factor for the tendency towards normalisation of glucose tolerance, hyperlipoproteinaemia and IRI-secretion, which could be registered in the intervention group after 2 years of observation. Following the preceding strong phase of diet, by Biguanides and Clofibrate a further significant improvement of the carbohydrate and fat metabolism could not be achieved. The decisive reserve in the treatment of obese maturity onset-diabetes could be seen in a permanent and continuous reduction of body weight. The results of this treatment depend highly on an intensive education as well as on frequent control of the patients' metabolism and their cooperation.

Lipoprotein pattern in long-term diabetes of an at least 35 years' duration. Results of the Erfurt Study.

All diabetic patients suffering from the disease for at least 20 years and living in the closed area of the Erfurt district in 1970 have been followed prospectively since that time. In 47 of them still alive in 1985, i.e. after more than 35 years of diabetes, serum lipid and apolipoprotein concentrations were measured and compared to those of non-diabetic subjects without cardiovascular diseases (n = 47) pair-matched by sex, age, and body weight. In males (n = 27) significantly (p less than 0.01) higher levels of HDL cholesterol and apolipoprotein A-I as well as lower concentrations of triglycerides and a lower total cholesterol/HDL cholesterol risk ratio than in nondiabetic control subjects could be found. In long-term diabetic females (n = 20), apolipoprotein A-I levels were also increased (p less than 0.02). Trends in HDL cholesterol and triglycerides were similar to those found in males but did not reach statistical significance. Higher concentrations of total cholesterol (p less than 0.02), LDL cholesterol (P less than 0.05), and apolipoprotein B (p less than 0.02), however, did not fit in with a beneficial lipoprotein pattern. The frequency of pathological lipoprotein patterns was not higher than among the non-diabetic control subjects (32% and 40%, respectively). According to these findings an antiatherogenic lipoprotein pattern might be considered, at least in males, as one of the determinants causing the multifactorial event of long-term survival in diabetes.