Epidemiology of insulin-treated diabetes mellitus in the East-German population: differences in long-term trends between incidence and prevalence rates.

In order to evaluate temporal trend variations of incidence and prevalence rates of Type 1 (insulin-treated) diabetes mellitus in the East-German population (19.6 million) 85,904 incidence cases, recorded by the Diabetes Registry between 1960 and 1989, were analyzed by calculating the regression coefficients for defined time intervals. The total incidence trend was characterized by a rise from 18/10(5) in 1960 to 29/10(5) in 1965, a decrease to 14/10(5) in 1975, and a slight increase to 15/10(5) in 1989. This trend was reflected only by patients with insulin treated diabetes mellitus aged > or = 30 yrs. Patients of the age groups 0-9 yrs., 10-19 yrs., and 20-29 yrs. exhibited increasing rates of 0.21/10(5)/year (1960-75), 0.22/10(5)/year, and 0.08/10(5)/year (1960-89), respectively. The rise in the prevalence rate from 187/10(5) (1960) to 658/10(5) (1989) demonstrated temporal trend variations during the periods 1960-71 (+19.3/10(5)/year), 1972-77 (-0.8/10(5)/year), and 1978-89 (+25.6/10(5)/year). The age-specific increasing prevalence trend varied between +0.81/10(5)/year (0-9 yrs.) and +48.89/10(5)/year (60-69 yrs.). The differences observed between incidence and prevalence trends were mainly due to changes in relative mortality rates of patients with insulin treated diabetes and the percentage of secondarily insulinized Type 2 diabetic patients. In summary, the incidence of Type 1 diabetes mellitus in East-Germany increased over the past 3 decades of registration by about 94% in children and adolescents, by 38% in adults aged 20-29 yrs., but not in people aged > or = 30 yrs.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival time after onset of diabetes: 29-year follow-up mortality study in a diabetes cohort from a rural district.

UNLABELLED: In order to evaluate various influences on survival time after onset of diabetes, a 29-year follow-up study was conducted in the 166 diabetic patients who were newly diagnosed between May 1st, 1962, and April 30th, 1963, in the rural district of Neustrelitz. Their mean age at onset was 63 (15-81) years, sex ratio was 2.5 (females: males). 27% of the patients were initially treated with insulin, 73% were on diet alone or on diet plus oral antidiabetic drug. There were 18 drop-outs. Check-up of mortality was performed at 3-year intervals. Shortening of life expectancy was calculated by comparison of their survival time to the life expectancy of the general population of the former German Democratic Republic with reference upon age and sex. RESULTS: Seven out of the remaining 148 study patients (4.7%) with an age at onset between 15 and 60 were alive. 19% of the patients had either reached or exceeded the life expectancy of the general population. The average loss in life expectancy in the decreased patients amounted to 5.3 years in males and to 6.4 years in females. The shortening of life expectancy decreased with increasing age at onset. Both underweight (BMI < 20) and extreme obesity (BMI > 40) were associated with a higher loss in life expectancy (14.7 vs. 10.8 yrs.) Also the survival time was not significantly different in dependence on the nature of treatment and on the circumstances of detection of the disease. CONCLUSION: only 19% of diabetic patients may expect a "normal" survival time.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes prevalence from health insurance data: evaluation of estimates by comparison with a population-based diabetes register.

UNLABELLED: At present in Germany, data on the prevalence of diabetes can only be obtained by modelling health insurance data. The National Diabetes Register of the former (East) German Democratic Republic which, between 1960 and 1990, monitored approximately 98% of all diabetic subjects, provides a tool for evaluating epidemiological estimates from other data sources. Therefore, the following data bases were compared for the year 1988: (1) a 5% random-sample (n = 6478) of all subjects insured at a local statutory health insurance company in the city of Dormund; (2) related data from the population-based diabetes register of former East-Berlin and (3) of the former German Democratic Republic. All data were standardized by sex and age according to the 1988 population statistics of the Federal Republic of (West) Germany thus resulting in the apparent diabetes prevalence of the Western part of Germany at that time. RESULTS: total prevalence rates were (1) 4.8%, (2) 4.9%, and (3) 4.4% (p < 0.05). The percentages of insulin-treated patients were (1) 18%, (2) 19%, and (3) 16%, respectively. 54% (1), 37% (p < 0.05) (2), and 42% (p < 0.05) (3), of the patients received oral antidiabetic drugs. It is concluded that the three samples are comparable and that the diabetes prevalence rates as estimated from health insurance data and from the two population-based registers give corresponding conclusions. Sample-based health insurance data may provide a useful and reliable tool for epidemiological studies on diabetes mellitus.

Different frequencies of diabetic complications in insulin-treated patients with diabetes of comparable duration, in relation to age at onset of diabetes.

Diabetic complications such as retinopathy and nephropathy affect the quality of life of diabetic patients. The aim of this study was to find out whether there are differences in the development of these complications associated with the age at onset of diabetes and the different effects of diabetes onset before, during or after puberty. Therefore, we tested the hypothesis whether onset of insulin dependent diabetes in puberty was connected with an increased risk of developing diabetic microangiopathy. We found a significantly increased risk in patients with diabetes onset in puberty up to a diabetes duration of 20 years if compared with diabetes onset before but not with that after puberty. It seems that diabetes onset before puberty delays the development of early diabetic complications and that changes of the hormonal status during puberty may be responsible for an earlier development of retinopathy. After about 20 years of diabetes there are no significant differences between the groups. Our results emphasize the necessity of early ophthalmological diagnosis and adequate metabolic control, especially in patients with diabetes onset during or after puberty, in order to prevent or delay the development of diabetic complications.

"Catheter-pens"--an alternative to insulin pump treatment?

Two types of insulin pens MADI and MD, were connected to subcutaneous catheters. These "catheter-pens" were used like hand-driven insulin pumps. Results after 1 year of treatment in 30 type 1 diabetics (HCP-negative; age at onset of diabetes 16.5 +/- 1.7 years; duration of diabetes 18.5 +/- 1.6 years, on multiple insulin injections before catheter-pen application): 1. better quality of life (reduction of frequency of needle pricks, more flexibility, inconspicuous application of insulin in public); 2. daily insulin--increased number of "injections" (4.2 +/- 0.1 vs 5.8 +/- 0.1, p less than 0.01), reduction of units per kg BW (0.70 +/- 0.02 vs 0.60 +/- 0.01, p less than 0.01), reduction of intermediate-acting insulin (14.1 +/- 1.3 vs 9.2 +/- 1.2 U/d, p less than 0.05); 3. no change of HbA1 (10.8 +/- 0.8 vs 10.2 +/- 0.2%, normal range 7.7 to 8.4%), mean blood glucose (MBG) in stress situation (8.4 +/- 0.4 vs 7.7 +/- 0.3 mmol/l), serum cholesterol and body weight, both within normal range; 4. improvement (p less than 0.05) of serum triglycerides, serum HDL-cholesterol, ratio of apolipoprotein A1/B; 5. rare skin reactions at the needle site. Conclusion. Catheter-pens offer a very convenient alternative for insulin administration in intensified conventional insulin treatment with multiple injections in type 1 diabetics.

Trends in mortality rates in the diabetic population of the GDR.

Based upon the National Diabetes Registry the mortality rates were assessed annually between 1961 and 1987 in the total diabetic population of the GDR. The rise of diabetes prevalence from 724/10(5) up to 3988/10(5) during the 27-year observation period was associated with an increase of relative mortality rates from 466% to 600% in insulin-treated diabetics, from 352% up to 528% in non-insulin-treated diabetics. By calculation of standardized mortality ratios (SMR) it could be shown that excess mortality is dependent on age but not at all on sex. Insulin-treated diabetics exhibited their maximum SMR of 650% to 750% at ages 25 to 45 years, while in non-insulin-treated diabetics the maximum SMR amounted to 450% at ages 25 to 35 years. In contrast to trends of the total relative mortality rates that of the overall age structure adjusted SMR of diabetics was characterized by a declining tendency, which may be a reflection of the improvement in diabetes care in our country, and which underscores the dependence of mortal, ty rates on the methods used for evaluation.

Frequency and therapy of end-stage renal disease due to diabetic nephropathy in the German Democratic Republic.

The prevalence of diabetic nephropathy among the German Democratic Republic (GDR) population is substantial, as is true of many other countries. An epidemiologic survey performed in the county of Neubrandenburg revealed increased creatinine values in 44.9% of diabetics with diabetes duration greater than 15 years, and in 24.9% of those with the disease less than 15 years. Given these data, the prevalence of renal insufficiency due to diabetic nephropathy is estimated as 27/100,000 in diabetics with greater than 15 years, and 9/100,000 in diabetics with less than 15 years of diabetes, including only patients up to the age of 49 years; this must be substantially greater when considering all age groups. Only 13% of all patients on chronic hemodialysis are diabetics. Although we offer each of our nephropathic diabetics such kidney replacement therapies as dialysis and transplantation, a substantial number of diabetics are not treated, presumably due to advanced macrovascular complications.

The progression of diabetic nephropathy in type I diabetics: relationship to metabolic control and blood pressure.

This study was designed to investigate the importance of risk factors such as hyperglycemia and elevated systolic and diastolic blood pressures on the progression of renal insufficiency in diabetics suffering from diabetic nephropathy. Seventeen patients with Type I, insulin-dependent diabetes mellitus (IDDM) (8 women and 9 men) undergoing chronic hemodialysis were investigated by retrospective follow-up and compared with 17 age and sex matched IDDM patients without diabetic nephropathy (controls). According to the time interval of creatinine increase from 200 to 600 mumol/l, the patients were divided arbitrarily into two groups with rapidly (group I less than 20 months) or slowly progressive (group II greater than or equal to 20 months) renal insufficiency. This period was 13.4 +/- 2.05 months in group I (age 36.67 +/- 2.47 years, diabetes duration 23.55 +/- 2.37 years) and 32.75 +/- 4.34 months in group II (age 40.62 +/- 2.63 years, diabetes duration 26.62 +/- 2.63 years, P.n.s.), respectively. The IDDM patients studied exhibited individually differing progressions of renal insufficiency at different times after manifestation of diabetes. After 15 years of diabetes duration, both risk factors, that is blood pressure and blood glucose concentrations, were elevated in nephropathic diabetics when compared with controls (p less than 0.01). During the phase of declining kidney function, mean blood pressures were found to be higher in IDDM patients with rapid progression of renal insufficiency when compared with slowly progressing diabetics. Although both risk factors were related to diabetic nephropathy, during the phase of renal insufficiency hypertension appeared to be more closely related to the further deterioration of kidney function.

Prevalence and incidence trends of non-insulin-dependent diabetes mellitus (NIDDM) in the population of the GDR.

Trends of prevalence and incidence rates of non-insulin-dependent diabetes mellitus (non-insulin-treated diabetes mellitus) were assessed in the population of the GDR based upon the National Diabetes Register and the Official Statistical Year Book as sources for the calculations. Within the 25-year follow-up period 1960-1984 the prevalence rose from 4.39%; to 31.95%; the incidence rate from 1.04%; to 3.57%. Age-dependence of the specific rates is characterized by their continuous rise above the age of 30 years reaching the peak prevalence of 146.6%; in 75- to 80-year-olds, that of 14.1%, for the incidence in people aged 70 to 75 years. A significant male preponderance was confirmed between the ages of 30 and 50 years, a significant overwhelming of female NIDDM in the age groups 60 to 90 years. Based on demonstrated correlations between the changes of living standard parameters and the epidemiological trend of NIDDM the conclusion is drawn that overnutrition and reduced muscular activity mainly account for the rise of diabetes morbidity in the population of the GDR.

In vivo comparison of different algorithms for the artificial beta-cell.

Using an extracorporeal artificial beta-cell in chronically diabetic dogs, the effects of four different mathematical models of glucose-controlled insulin dosage were compared: the Biostator algorithm (quadratic equation), Toronto algorithm (hyperbolic tangent function), Karlsburg algorithm (modified first-order derivative controller), and Ilmenau algorithm (second-order linear difference equation). The constants of all formulas implemented for the artificial beta-cell were obtained by regression analysis of paired blood glucose and plasma insulin data from normal control animals. Thus, they were biologically equivalent for all formulas. The patterns of blood glucose, insulin doses, and plasma insulin before, during, and after an intravenous glucose infusion test performed during the glucose-controlled insulin infusion showed no significant differences between the experimental groups subjected to the different algorithms. However, in no case were really normal blood glucose response curves restored by the artificial beta-cell. This might be due, first, to the fact that the algorithm parameters were not adapted to the actual individual insulin responsiveness, second, to the unphysiological peripheral venous route of insulin administration, and, third, to the lack of appropriate adaptation of the animals to normoglycemia.

[Measurement of uteroplacental circulation with 113m indium in diabetic pregnancy]. / Die Messung der uteroplazentaren Durchblutung mit 113m In in der diabetischen Schwangerschaft.

In 122 diabetic pregnancies the placental blood flow has been estimated determining the half life of the activity inflow (2 MBq 113 m In labelled transferrin) into the placental bed. We used a highly sensitive detector (modified pinhole collimator) and a computer supported evaluation, free from subjective influences. 259 flow measurements were compared to the risk of complication in the course of a diabetic pregnancy. - The half life values in the diabetic group, calculated by a gamma camera computer system by means of an iterative regression analysis, were significantly different compared to a control group (12 pregnancies without risk.) - Severe diabetic angiopathic complications (White classes D, F, and R) are accompanied by higher half life values (placental blood flow reductions) and perinatal complications. - Even in pregnant women with gestational diabetes or disturbances of the carbohydrate metabolism a disturbed placental hemodynamic is to be found.

Long-term improvement in metabolic control of unstable type I diabetes by s.c. insulin injection patterns based on the dose profiles required by bed-side artificial beta-cell.

Twenty unselected unstable type I diabetic inpatients whose blood glucose control was insufficient employing three daily s.c. injections of regular insulin supplemented by intermediate acting insulin were subjected to a 48-hour treatment with the Biostator -GCIIS when both diet and muscular exercise were kept as close as possible to the conditions at home. The s.c. injection regimen was adjusted to the insulin dose pattern required by the artificial beta cell. There was significant metabolic improvement in 16 out of the 20 patients on discharge, in comparison to the pre-Biostator conditions. This improvement was still present when the patients were re-admitted after an average of seven months. It is concluded that in certain cases of unstable type I diabetes mellitus the metabolic re-arrangement based on intercalary days on an extracorporal artificial beta cell might be useful if the control constants are adapted to minimize the insulin requirement by the machine.

Methods and effects of improved conventional insulin treatment in labile insulin-dependent diabetes (IDDM).

In 92 particularly unstable IDDM patients we have tried to avoid any gap in daily insulin supply by applying one out of four newly designed combinations of regular and depot insulin. The short-term effect after three weeks and the long-term effect after greater than or equal to 12 months (data from 30 patients only) of these new regimens were compared with those of the traditional regimen in a retrospective evaluation: Glycemia (level and excursions) was significantly improved both after three weeks of inpatient treatment and after greater than or equal to 12 additional months on outpatient regimen. Serum beta-LP and HbA1 showed slight decrease during long-term follow-up. The majority of the patients reported improved well-being under conditions of daily life. However, the glycemia achieved was still far from the permanent euglycemia aimed at. For the avoidance of any gap in insulin supply in labile diabetics four insulin injections are necessary in most cases. For this, individually tailored combinations of regular and depot insulin must be drawn up carefully together with the patients to avoid a " strait -jacket" system which would not work under conditions of daily life.

Estimation of individually adapted control parameters for an artificial beta cell.

For optimum long-term glycemic regulation using a miniaturized artificial beta cell it is indispensible to estimate control parameters suited to the individual requirements of each diabetic patient. To solve this problem, a strategy has been developed which is based on engineering optimum-control theory with a model involving glucose and insulin interactions. The model considers physiologically relevant unit processes like endogenous glucose production, insulin-independent glucose uptake from its apparent distribution space, insulin-dependent glucose utilization, glucose-dependent insulin supply, and insulin catabolism. The assumed model structure is validated by results obtained in experimentally diabetic dogs using partition analysis. The individual parameter values of the model are obtained by a digital computer procedure based on a simple test which involves a bolus injection of glucose + insulin when a constant basal insulin dose is being administered in the diabetic in whom normoglycemia was re-established before the test. The method presented is recommended for future use in all cases where an optimized insulin regimen is to be worked out.

Modelling the glucose-insulin system as a basis for the artificial beta cell.

The control constants for glucose-dependent insulin dosage in diabetic dogs were determined from test results in the opened system on the basis of a global blood glucose plasma-insulin control model. The controlled plant of the model consisted of the glucose and insulin subsystems; the entire insulin providing process was considered to be the controlling element, and the glucose-dependent insulin dose estimation, the controller. The constants obtained were employed in the extracorporeal artificial beta cell. The structure of the model and the numerical values of its state variables were verified by the prediction of blood glucose responses to intravenous glucose loads and by the correspondence between glucose balances and insulin doses as calculates and those as observed in diabetic animals. The application of the optimum control constant estimates in feedback-controlled insulin infusions provides improved blood glucose patterns but unchanged needs for insulin in comparison to the application of standard control parameters.

[Effect, on the newborn infant, of carbohydrate metabolism in pregnancy in insulin-dependent diabetics]. / Der Einfluss des Kohlenhydratstoffwechsels während der Schwangerschaft insulinabhängiger Diabetikerinnen auf das Neugeborene.

The influence of the moment in pregnancy of insulin dependent diabetic women, at which normoglycemia by insulin therapy could be reached, on cord blood insulin concentration and neonatal morbidity was investigated. There is a positive correlation between the moment of normoglycemia (HbA1-values less than or equal to 8.5%) and the insulin concentration and furthermore the incidence of respiratory distress syndrome and macrosomia in the newborn. It is concluded that a tight metabolic control in insulin dependent diabetic women already prior to or early in pregnancy (at least until the 16th week) will be able to decrease the incidence of morbidity in infants of diabetic mothers.

Ergometric heart rate, blood pressure and work capacity (PWC170) in type I diabetics with diabetes-specific microangiopathy.

118 male and 68 female type I diabetics and 25 male and 23 female nondiabetic healthy controls were compared during submaximal bicycle ergometer tests using four work stages (duration: 6 min each) of 50 W, 75 W, 100 W and a submaximal stage producing a heart rate of 170 min-1. We found that male type I diabetics with and without retinopathy who had significantly higher than normal heart rates both at the start and during the ergometer test also had above normal ergometric blood pressures. Female type I diabetics, in contrast, did not differ significantly from the controls in terms of heart rate before and during the ergometer tests. The PWC170 of all male type I diabetics was, in contrast to that of the female patients, lower than that of the controls. In diabetics with diabetic nephropathy there was no correlation between exercised acceleration of the heart rate and the degree of nephropathy despite their higher heart rates at the beginning and during the ergometer test, but a correlation was found between the ergometrically increased blood pressure and the severity of the diabetic nephropathy. In male type I diabetics cardiocirculatory adaptation to muscular work was reduced, and this reduction became more marked as the degree of diabetic microangiopathy increased. Compared with the controls, the increase in systolic blood pressure evoked by activity on the ergometer in male and female type I diabetics was disproportionate to the actual load and correlated with the degree of diabetic microangiopathy.