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Objective: A reduction of diabetes-related amputations by at least one-half within 5 years was declared a primary objective for Europe (St. Vincent Declaration, 1989). We collected data about incidence rates of amputations in one German city (Leverkusen, with a population of approximately 160,000 inhabitants) between 1990 and 1998 to ascertain a potential change in rates of incidence., Research Design and Methods: From all three hospitals in Leverkusen, we obtained complete lists of lower-limb amputations. From each patient record, diabetic status was determined. Only the first observed amputation was counted for the analysis. We estimated incidence rates of amputations in the entire population, the diabetic population, and the nondiabetic population. To test for time trend, we fitted Poisson regression models, adjusting for age and sex., Results: During, the defined period (the years 1990, 1991, and 1994-1998), 339 patients (all residents of Leverkusen) without previous amputations had nontraumatic lower-limb amputations. Of all subjects. 46% were female. Moreover, 76% of the subjects were known to have diabetes. Mean age was 71.3 years. Incidence rates in the diabetic population (standardized to the estimated German diabetic population, per 100,000 person-years) were as follows: 1990, 549; 1991, 356; 1994, 544; 1995, 386; 1996, 426; 1997, 433; and 1998, 463. The Poisson models showed no significant change of incident amputations over time in the diabetic population or in the nondiabetic population., Conclusions: Beyond random variation, no change of incidence rates could be observed over the past 9 years. More specific interventions are needed to achieve a substantial reduction of diabetes-related amputations.

Before any treatment of type 2 diabetes in accordance with the principles of evidence-based medicine can be generally recommended, the considerable disease heterogeneity must be taken into account, and randomized controlled intervention trials directed to cardiovascular and microangiopathic organ damage end points must be performed for the various subgroups of patients. Until then, it appears prudent to treat the typical Caucasian type 2 diabetic patient primarily by nondrug therapies, and if they fail to achieve the patient's individual treatment goals, then insulin treatment should be initiated. Treatment of type 2 diabetic patients with insulin alone, aimed at the patient's individual therapeutic goals, is effective and safe when conducted as an integral part of specific and structured treatment and teaching programs. Insulin treatment can be safely used to achieve near-normal HbA1c levels (< 7.0-7.5%) if prevention of diabetic microangiopathy is indicated, or to maintain HbA1c levels < 8.5-9.0% if catabolic symptoms due to insulin deficiency are to be prevented.

This contribution describes the nationwide implementation of an intensive treatment and education program for type 1 diabetic patients in the clinical routine of the German health care system. Based on the formation of a working group (Arbeitsgemeinschaft Strukturierte Diabetestherapie [ASD]) of presently 57 general internal medicine departments, mainly from secondary and tertiary care levels in city and country hospitals throughout the country, a peer-review quality circle was formed as an official working group of the German Diabetes Association. The participating institutions performed a structured program of intensive treatment and education in all type 1 diabetic patients referred to them on a routine basis. The program includes multiple daily insulin injections or continuous subcutaneous insulin infusion, several times daily blood glucose self-monitoring and self-adaptation of insulin dosages and other aspects of treatment by the patients, and a far-reaching liberalization of the nutrition regimen. The group has attempted to document and to improve the quality of the structure and process of type 1 diabetes care in its participating institutions by a system of peer supervision. Furthermore, all member institutions volunteered to collect outcome data based on systematic 1-1.3 years' follow-up examinations of consecutive type 1 diabetic patients. For the 1997 evaluation of 1,103 type 1 diabetic patients, significant decreases of GHb levels and of incidence rates of severe hypoglycemia (from 0.35 to 0.16 cases per patient-year) and ketoacidosis (from 0.08 to 0.02 cases per patient-year) are presented. The ASD quality circle represents a model to improve principal aspects of type 1 diabetes care on a nationwide basis.

Objective: To validate a diabetes-specific quality-of-life scale and to assess its psychometric properties in a large sample of patients with type 1 diabetes., Research Design and Methods: To assess the quality of diabetes care in a population-based study, a representative sample of 684 patients with type 1 diabetes was examined. A total of 657 patients (42% female; mean age 36 years; mean diabetes duration 18 years) completed the diabetes-specific quality-of-life scale (DSQOLS), which comprised 64 items on individual treatment goals (10 items), satisfaction with treatment success (10 items), and diabetes-related distress (44 items). Statistical examinations covered factor analysis, internal consistency of subscales, and construct and discriminant validity., Results: Factor analysis of the 44 items on diabetes-specific burdens revealed six reliable components (Cronbach's alpha): social relations (0.88), physical complaints (0.84), worries about future (0.84), leisure time flexibility (0.85), diet restrictions (0.71), and daily hassles (0.70). All six subscales were significantly correlated with a validated well-being scale (r = -0.35 to -0.53, P < 0.001) and treatment satisfaction (r = 0.28 to 0.43, P < 0.001). Physical complaints (r = 0.24) and worries about future (r = 0.17) showed the highest correlations with HbA1c (P < 0.001). A flexible insulin therapy, a liberalized diet, the absence of late complications, and a higher social status were significantly associated with more favorable scores in different domains., Conclusions: The DSQOLS is a reliable and valid measure of diabetes-specific quality of life. The scale is able to distinguish between patients with different treatment and dietary regimens and to detect social inequities. Use of the DSQOLS for assessment of individual treatment goals as defined by the patients may be helpful to identify motivational deficits and to tailor individual treatment strategies.

Objective: A reduction of diabetes-related blindness was declared a primary objective for Europe (St. Vincent Declaration). We collected data about incidence rates of blindness in the diabetic population compared with the nondiabetic population. Up to now, such data are scarce-even worldwide., Research Design and Methods: A complete list of newly registered blindness allowance recipients was drawn up in the district of Württemberg-Hohenzollern, Germany, between 1990 and 1993. From these data, we estimated age-specific and standardized incidence rates of blindness in the entire, the diabetic, and the nondiabetic population, as well as relative and attributable risks due to diabetes., Results: There were 2,714 people meeting the inclusion criteria; 1,823 (67.2%) were female and 781 (28.8%) had diabetes. In 318 subjects, diabetes was likely to be the only cause of blindness; in 192 subjects, it was one of several contributory causes. Age of women was 73.9 +/- 19.4 years (mean +/- SD) and of men 63.3 +/- 25.5 years. Results standardized to the (West) German population are as follows: incidence rates (per 100,000 person-years): total population: 13.5; diabetic population: 60.6; nondiabetic population: 11.6; relative risk: 5.2; attributable risk among exposed: 0.81; and population attributable risk: 0.14. The relative risks decreased considerably with increasing age. When the study is repeated to monitor the St. Vincent targets, a reduction in the incidence rate of blindness in the diabetic population by 17% will be detected with 95% power., Conclusions: Great relative and attributable risks, especially in younger age-groups, indicate the need for increased attention to preventive measures for microvascular complications.

Objective: We collected data on the incidence rates of amputations and their relative risk in diabetic subjects compared with the nondiabetic population., Research Design and Methods: From all three hospitals in a city of approximately 160,000 inhabitants, we obtained complete lists of nontraumatic lower limb amputations. From each patient record, diabetic status was determined. We estimated age-specific and standardized incidence rates of amputations in the diabetic and nondiabetic populations and in the entire population, as well as the relative and attributable risks due to diabetes., Results: Nontraumatic lower limb amputations were performed on 106 residents of Leverkusen (Germany) in 1990 and 1991. Of them, 82 (77.4%) had diabetes. Mean age was 72.0 years. In the case of multiple amputations, only the highest level was counted for the analysis. The following results were standardized to the German population. Incidence rates (100,000(-1) year-1) were determined to be as follows: for all amputations per total population, 33.8; for amputations in diabetic individuals per diabetic population, 209.2; for amputations in nondiabetic individuals per nondiabetic population, 9.4. Relative risk was 22.2; attributable risk among exposed, 0.96; population attributable risk, 0.72. When the study is repeated to monitor the St. Vincent targets (50% reduction), a reduction in the amputation rate in the diabetic population by 46% will be detected with 90% power., Conclusions: We found incidence rates similar to those in the non-Indian population of the U.S. Great relative and population-attributable risks indicate that improving foot care in diabetic individuals appears to be the main target for the reduction of amputations in the general population.

Objective: To investigate the association between cigarette smoking and the progression of diabetic nephropathy., Research Design and Methods: A prospective, follow-up study over one year was conducted in a sequential sample of 34 smokers, 35 nonsmokers, and 24 ex-smokers with type I diabetes, hypertension, and diabetic nephropathy. Progression of renal disease was defined according to the stage of nephropathy as an increase in proteinuria or serum creatinine or a decrease in the glomerular filtration rate., Results: Progression of nephropathy was less common in nonsmokers (11%) than in smokers (53%) and patients who had quit smoking (33%), P < 0.001. In a stepwise logistic regression analysis, cigarette pack years, 24-h sodium excretion, and GHb were independent predictive factors for the progression of diabetic nephropathy. Because blood pressure (BP) was well controlled in these patients and most values were within a normotensive range, neither standing, sitting, nor supine BP values were associated with progression of nephropathy., Conclusions: Cigarette smoking represents an important factor associated with progression of nephropathy in treated hypertensive type I diabetic patients.

Objective: To evaluate the long-term effectiveness and safety of a copper intrauterine device fulfilling modern standards in type I diabetic women compared with nondiabetic women., Research Design and Methods: Type I diabetic women (n = 59, age 27 +/- 5 yr, duration of diabetes 12 +/- 8 yr, HbA1c 7.0 +/- 1.2%, 78% nulliparous women) were prospectively evaluated at 3, 6, 12, 24, and 36 mo by a gynecological exam and a standardized questionnaire after insertion of the intrauterine device (CU Safe 300, 300 mm2 of copper). A group of nondiabetic women (n = 1150) of comparable age and parity evaluated according to the same study protocol served as a control group., Results: In the diabetic women (1754 cumulative months of use), events leading to termination of the intrauterine device during the 1st yr (691 women-mo) were one accidental pregnancy, one expulsion, one removal for pain, two removals for bleeding, and one removal for planned pregnancy. Events during the 2nd (593 women-mo) and 3rd yr (470 women-mo) were zero and one accidental pregnancy., one and two removals for bleeding, one and one removal for pain, one and one removal for other medical reasons, and two and two removals for planned pregnancy, respectively. No case of pelvic inflammatory disease was diagnosed in the diabetic group, and one case was diagnosed in the nondiabetic group (28,369 mo of cumulative use). Events leading to termination of the intrauterine device per women observed per year and continuation with the intrauterine device after each year of use were comparable in the diabetic and nondiabetic groups for the 1st, 2nd, and 3rd yr., Conclusions: These results, although preliminary because < 100 diabetic women were studied, indicate that the intrauterine device CU Safe 300 is as effective, safe, and well-tolerated in diabetic as in nondiabetic women. Specific objections to the use of intrauterine devices in type I diabetic women do not seem to be justified for modern, copper-mediated models.

Objective: To evaluate the incidence and predisposing factors of severe hypoglycemia (SH) in pregnant women with insulin-dependent (type I) diabetes mellitus., Research Design and Methods: SH (impairment of consciousness due to hypoglycemia subsequently treated with glucagon or i.v. glucose) was recorded in all pregnant type I diabetic women (n = 77) who attended our pregnancy clinic during 85 pregnancies from 1986 to 1990., Results: Ninety-four SHs were reported during 35 pregnancies. Of 94 SHs, 84% occurred before the 20th gestational wk (median 12th wk) and 77% during sleep. In the group with SH, there was no permanent maternal sequelae, and there was a favorable fetal outcome (no perinatal death and no congenital malformation). Mean HbA1c values were not different between the group with and without SH for the first half (6.4 +/- 1.1 vs. 6.3 +/- 0.9%) and 2nd half (5.4 +/- 0.6 vs. 5.5 +/- 0.7%) of pregnancy. The percentage of women with SH before pregnancy (51 vs. 28%, P less than 0.05) and the incidence of SH patients before pregnancy (0.49 vs. 0.08 SH/patient/yr) was different between the group with and without SH., Conclusions: SH is frequent during pregnancies of type I diabetic women with near normoglycemia. The risk for SH is particularly pronounced during the first half of pregnancy and in women with a history of SH.

Objectives: To compare hypoglycemic warning symptoms (main objective) and incidence of severe hypoglycemia (secondary objective) between patients treated with animal and human insulin preparations., Research Design and Methods: Two hundred forty-seven patients on treatment with animal insulin preparations and 276 patients on human insulins, matched for duration of diabetes (16 +/- 11 vs. 15 +/- 10 yr), were recruited for the study. Patients were interviewed with a standardized questionnaire., Results: When asked which symptom usually occurs first during hypoglycemia, 19% of the animal insulin group and 22% of the human insulin group answered "sweating," 19 and 17%, respectively, answered "trembling," and 15 and 11%, respectively, answered "unrest." According to the patients' perception, in both groups, their most reliable hypoglycemic warning symptoms were "trembling" (26 and 22%) and "sweating" (15 and 18%). Six and eight percent of patients, respectively, reported hypoglycemia unawareness and 17 and 18%, respectively, impaired awareness of hypoglycemia. The incidence of severe hypoglycemia was 0.45 cases/patient-yr in patients treated with animal insulins and 0.46 cases/patient-yr in patients treated with human insulin preparations. The differences were not statistically significant., Conclusions: This study shows that hypoglycemic warning symptoms and the incidence of severe hypoglycemia are comparable between patients on treatment with human and animal insulin preparations.

Objective: To assess the frequency and possible risk indicators of severe hypoglycemia in insulin-dependent (type I) diabetic patients with impaired kidney function., Research Design and Methods: Retrospective follow-up examination of case subjects and control subjects with mean follow-up periods of 2.9 and 1.3 yr, respectively. The setting was the diabetes center at the Düsseldorf University hospital. Subjects were consecutive type I diabetic patients. Case subjects consisted of 44 patients with initial serum creatinine levels of greater than or equal to 133 microM and pathological proteinuria. Control subjects consisted of 46 patients with normal serum creatinine levels matched for age, duration of diabetes, and hypertension; 57% of case subjects and 67% of control subjects were being treated with beta-blockers. Incidence of severe hypoglycemia (cases/patient-yr) was assessed through an interviewer-administered questionnaire., Results: At comparable levels of HbA1c (7.9 +/- 1.8 vs. 7.6 +/- 1.1%), case subjects had a fivefold higher incidence of severe hypoglycemic episodes (1.28 vs. 0.25 cases/patient-yr, P less than 0.02) than control subjects. Within the group with impaired kidney function, patients with severe hypoglycemic episodes had lower HbA1c levels (7.4 +/- 1.6 vs. 8.7 +/- 2.0%, P less than 0.03) and a lower body mass index (22.0 +/- 3.4 vs. 24.4 +/- 3.8 kg/m2, P less than 0.04) than those without severe hypoglycemic episodes, whereas serum creatinine levels, body weight-related insulin dosage (U x kg-1 x day-1), prevalence of blindness, autonomic neuropathy, and treatment with beta-blockers were comparable., Conclusions: Type I diabetic patients with impaired kidney function are at an excessively high risk of severe hypoglycemia. In addition to low HbA1c levels, a low body mass index appears to be a risk indicator for this adverse effect of insulin therapy.

Objective: To determine the importance of color discrimination ability regarding accuracy in the self-monitoring of blood glucose., Research Design and Methods: Two hundred two insulin-dependent (type I) diabetic patients performed the Fansworth-Munsell 100-hue test and a second group of 159 type I diabetic patients performed a new Düsseldorf 26-hue test. Error scores in both tests were compared with error scores of patients' self-monitoring of blood glucose measurements with Chemstrip Haemoglucotest 20-800 strips., Results: Color discrimination ability decreased with age, diabetes duration, and presence of retinopathy. It was independent of the degree of glycemia and accuracy of self-monitoring of blood glucose., Conclusions: Impaired color vision by itself is no reason to abandon self-monitoring of blood glucose with visually read strips.

In 10 type I diabetic outpatients treated by continuous subcutaneous insulin infusion (CSII), dietary habits and metabolic control were investigated. Under conditions of a conventional diabetes diet (including 5-6 meals per day and a strictly planned meal intake) as well as under a "less restricted diabetes diet" (e.g., free choice of number, timing, and amount of carbohydrate intake) near normoglycemia could be achieved. Mean daily blood glucose levels did not change significantly when the patients' nutrition was alternated between both diets. During the "less restricted diabetes diet," the patients opted for a rather high fat intake (51 +/- 5% fat, 34 +/- 5% carbohydrate, and 15 +/- 2% protein). Despite this unintended dietary behavior, serum lipids and body weight remained normal after an observation period of 4-6 mo. It is concluded that during permanent near normoglycemia achieved by CSII a partial liberalization of the diabetes diet does not introduce any short-term or long-term metabolic risk factors for cardiovascular diseases.

Absorption kinetics of subcutaneously injected human insulin (recombinant DNA) and semisynthetic human regular insulin were investigated and compared to the respective porcine insulin preparations in normal volunteers. The absorption of all regular human insulin preparations tested was accelerated as compared to porcine insulins. The clinical relevance of these findings in regard to the treatment of diabetes mellitus appears to be doubtful. As for mixtures of porcine regular and intermediate-acting insulin preparations, the absorption of human regular insulin is not altered when mixed with intermediate-acting human insulin.

The CR3-45 NM Canon nonmydriatic fundus camera detects relevant diabetic retinopathy with high sensitivity. To determine whether examination of one eye per patient would suffice for screening purposes, 473 pairs of standard 45 degree fundus Polaroid prints obtained with the Canon camera were assessed from 167 patients with and 306 without diabetic retinopathy. On the basis of considering only one eye per patient, absence of retinopathy would have been diagnosed in 336 patients, with 9% of the diagnoses false negative. One hundred thirty-seven of the 167 patients with retinopathy in at least one eye would have been diagnosed correctly by considering one eye per patient (sensitivity 82%, specificity 100%). Thus, a standard 45 degree fundus Polaroid print from one eye per patient may suffice for screening purposes if the picture is free from diabetic abnormalities. Otherwise, both eyes should be examined immediately, and the patient should be referred to an expert ophthalmologist who specializes in diabetic retinopathy for confirmation of the diagnosis and staging of diabetic retinopathy status.

We developed a computer program for the simulation of plasma insulin and glucose dynamics after subcutaneous injection of insulin. The program incorporates a pharmacokinetic model to calculate the time courses of plasma insulin for various combinations of popular preparations (regular, NPH, lente, and ultralente). With the use of a pharmacodynamic model describing the dependence of glucose dynamics on plasma insulin and glucose levels, the program can predict the expected time course of plasma glucose in response to a change in carbohydrate intake, insulin dose, timing, or regimen. A set of typical parameters has been obtained by analysis of data from the literature. The results of several computer simulations are presented showing the effect on a 24-h insulin and glucose profile of systematically changing insulin regimen, dose, timing of meals, or timing of preprandial insulin administration. The program can be used to explore on a theoretical basis the impact of various factors associated with glycemic control in insulin-dependent diabetes mellitus. As an educational tool, the program provides a realistic environment for demonstration of the combined or isolated effects of insulin and diet on glycemia.

This paper describes systematic studies on the absorption kinetics of exogenous insulin from its subcutaneous tissue depot in 52 male nonobese volunteers (age 20-30 yr). Five experimental protocols were used: effect of changing injection site, effect of temperature change and local massage, effect of aprotinin and human serum, effect of mixing regular insulin with long-acting insulin preparations, and effect of temperature change, muscular exercise, and local massage on the absorption of long-acting insulin preparations. The fastest absorption of insulin occurred at the abdominal injection. Absorption after arm injection was faster than after thigh injection. A hot bath and local massage dramatically increased serum insulin levels in the first 90 min after injection; in contrast, a cold bath delayed absorption substantially. Both aprotinin and the subjects' own blood serum mixed with insulin caused a marked acceleration of the insulin absorption process. Absorption kinetics of two neutral regular insulins (Actrapid and Leo Regular) were virtually identical. Mixing Actrapid with Monotard caused higher serum insulin levels than the mixture of Leo Regular with NPH. A time lag of 5 min between the mixing of Actrapid and Monotard and the injection caused a delayed rise of serum insulin levels; in contrast, this delay could not be observed when Leo Regular and NPH were mixed. Volunteers performed bicycle exercise, applied a hot water bottle to the injection site, or rubbed the injection site 2 1/2 h after injection of long-acting insulin. Accelerated absorption of insulin was only observed after local massage of the injection site of Monotard, Leo NPH, and Mixtard. Local heat had no effect. Exercise caused only an increased absorption of insulin after the Mixtard injection but not after Monotard or NPH injection. These findings have clinical significance and should not be without potential benefit in the attempt to improve metabolic control in insulin-treated diabetic patients.

Pharmacokinetics and bioavailability of 1 mg glucagon injected intramuscularly (i.m.), subcutaneously (s.c.), or intravenously (i.v.) were studied in 6 nondiabetic men rendered hypoglycemic by s.c. injection of 10 U regular insulin. At 90 min after the insulin injection, when blood glucose levels had fallen to a mean of 49 mg/dl, glucagon was administered. Ten minutes later plasma glucagon levels had risen from a mean of 246 to 3233 pg/ml (s.c. experiment) and from 250 to 2638 pg/ml (i.m. experiment). Accordingly, there was no difference in blood glucose behavior whether glucagon was injected s.c. or i.m. In the i.v. experiment, plasma glucagon levels were significantly higher during the first 15 min after the glucagon injection when compared with the other experiments. The initially high levels of plasma glucagon after i.v. administration were associated with a steeper rise of glycemia during the first 5 min after glucagon injection; the maximal increase of blood glucose was, however, not different when compared with the s.c. or i.m. route of glucagon administration. Thus, in case of severe hypoglycemia, therapeutically administered glucagon will be most efficient when injected i.v., but there is no difference between the i.m. and s.c. routes of administration with regard to the efficacy to increase blood glucose levels.

Forty unselected type I (insulin-dependent) diabetic patients with insulin pumps were examined three times for cutaneous complications and bacterial colonization of their subcutaneous catheter needles. Fifty-eight of the 120 needles were contaminated, 42 of them with Staphylococcus epidermis. Cutaneous complications, i.e, erythema of greater than or equal to 1-mm diam at the needle-insertion site, were seen with similar frequency. Significantly fewer (P less than .001) cutaneous complications and contaminated needles were found when a disinfectant was sprayed on the skin before insertion of the needle. The results indicate that infection along the indwelling subcutaneous needle contributes substantially to cutaneous complications during continuous subcutaneous insulin infusion and that these complications can successfully be prevented by appropriate antiseptic measures.

The risk of severe hypoglycemia associated with the particular therapeutic approach of two University hospitals was assessed in 96% of all patients with insulin-dependent diabetes mellitus (IDDM) who had been admitted during a period of almost 3 yr to the diabetic wards of two hospitals and who participated in a structured teaching and treatment program. During a mean follow-up period of 18 mo, 10% of the conventionally treated patients (N = 384; age 30 +/- 13 yr; duration of diabetes 12 +/- 9 yr) and 9% of the CSII-treated patients (N = 50, age 28 +/- 7 yr, duration of diabetes 13 +/- 7 yr, total follow-up period 1093 patient-mo) experienced at least one severe hypoglycemic episode per year, and a total of 123 severe hypoglycemic episodes occurred. In a subgroup of 169 conventionally treated patients, mean glycosylated hemoglobin values decreased from 10.5 +/- 1.9% before participation in the program to 9.2 +/- 2.0% (P less than 0.001) 18 +/- 4 mo thereafter. For the CSII-treated patients, glycosylated hemoglobin values were 9.7 +/- 1.9% before initiation of pump therapy and remained at the upper normal range from 3 mo thereafter throughout the study. There was no relationship between glycosylated hemoglobin levels and the occurrence of severe hypoglycemic episodes. Fifty-three severe hypoglycemic episodes were treated with glucagon injections by the patients' relatives (all but one effectively), 30 were managed by assisting physicians, and 44 led to hospitalization. Thus, successful attempts to improve glycosylated hemoglobin values in an unselected group of patients with IDDM were not associated with an unduly high risk of severe hypoglycemia when compared with the scarce data from the literature.

The absorption kinetics of human insulin (Novo) were studied and compared with those of purified porcine insulin preparations in seven healthy men. The absorption of insulin after subcutaneous injection of human insulin (Actrapid, Novo) was significantly accelerated and its hypoglycemic effect significantly stronger when compared with porcine insulin (Actrapid). No differences in the absorption kinetics were observed using human insulin (Monotard, Novo) and porcine insulin (Monotard) preparations, respectively. A clinical trial was designed to determine whether the pharmacokinetic differences were relevant for the clinical use of regular human insulin. The efficacy of human and porcine insulin (Actrapid) was tested in a double-blind crossover protocol in 12 type I diabetic patients treated with continuous subcutaneous insulin infusion. Near-normoglycemia was achieved with both types of insulin. Diurnal blood glucose values and excursions, insulin requirements, the frequency of mild hypoglycemic episodes, and the carbohydrate content of the diet were essentially identical. Thus, the differences between the absorption of human insulin and porcine regular insulin from a subcutaneous depot as observed in the pharmacokinetic studies in normal man do not appear to be relevant in the clinical practice of the subcutaneous insulin replacement therapy in type I diabetes mellitus at near-normoglycemia.

We examined the reliability of split test strips for blood glucose self-monitoring. One hundred visual readings were performed with each of the following test strips: original Haemoglukotest 20-800 (HGT 1/1; Boehringer-Mannheim, Mannheim, FRG) and Haemoglukotest 20-800 halved either by a splitting device (HGT 1/2 SP) or by a pair of scissors (HGT 1/2 SC). Within the plasma glucose range of 20-360 mg/dl, there was a close correlation between the results of all three test-strip readings and the values obtained by the reference method (Beckman glucose analyzer): HGT 1/1, r = .950; HGT 1/2 SP, r = .966; and HGT 1/2 SC, r = .966. Absolute deviations from the reference values were 17 +/- 2, 17 +/- 1, and 17 +/- 1 mg/dl (mean +/- SE). Analysis of variance did not reveal any significant differences between the values of each of the three procedures compared with the reference method (P = .98). These results indicate that visual reading of split test strips is as reliable as the reading of original test strips. A special splitting device is not necessary. Diabetic patients should be advised to use split test strips for blood glucose self-monitoring to reduce costs.

The biologic potency (plasma glucose depression) of pancreatic human insulin was compared with that of biosynthetic human insulin (BHI), manufactured by recombinant DNA techniques in bacteria, following intravenous injection in rats. The specific activity of the pancreatic human insulin was 32 U/mg, while that for BHI was 27 U/mg. These values were not significantly difference, but were higher than the value for pancreatic pork insulin (25 U/mg). The pharmacokinetics of i.v. injected A14-mono-125I-insulin (pork) were found to be similar to those observed for semisynthetic [3H]insulin (pork), the respective metabolic clearance rates (MCR) being 20.8 +/- 0.8 ml/min/kg (N = 4) and 23.6 +/- 1 ml/min/kg (N = 5) (P greater than 0.1). The MCR for A14-mono-125I-BHI was 24.6 +/- 2.2 ml/min/kg (N = 4), which was significantly higher (P less than 0.025) than the value for A14-mono-125I-pork insulin. BHI is thus no less active than pork insulin in rats and possibly somewhat more active. The small difference in activity may be due to increased affinity for rat insulin receptors, resulting in a more rapid MCR for BHI. In addition, the A14-monoiodinated insulin tracer used in these studies is indistinguishable from semisynthetic [3H]insulin in terms of its rate of clearance, indicating that the insulin molecule has not suffered any iodination damage and is thus a valid tracer for metabolic and receptor studies.

In search of possible interactions between plastic tubings used for insulin-pump treatment and commercial regular insulin preparations, various catheter sets made from polyvinyl chloride (PVC), polyethylene (PE), and nylon plastics were perfused at 30 degrees C in a laboratory setting for up to 72 h. The perfused insulin solutions were analyzed by high-performance liquid chromatography and atomic absorption spectroscopy. Although no plasticizer, e.g., dioctyl phthalate, or nickel or chromium ions were found in the perfusates, substantial interactions between the plastics and the insulin solutions were detected, extraction of bacteriostatic additives from the insulin solutions in particular. The PVC retained up to 88% of the bacteriostatics from the insulin preparations, whereas PE tubings retained only 10-15%. Whether the loss of preservatives during perfusion through PVC catheters predisposes to cutaneous infections during insulin-pump therapy remains to be shown.