The aim of this article is to critically discuss the technical and clinical aspects of glucose sensors and to briefly review current technical developments. This includes sensors for spot glucose measurements as well as those used for continuous glucose monitoring. Continuous glucose monitoring in particular should supply the diabetic patient with all the information required to optimize insulin therapy and metabolic control. Such systems should also allow hypo- and hyperglycemic episodes to be avoided. During the last 30 years numerous attempts have been made to develop glucose sensors, and new major breakthroughs have been announced repeatedly. However, up until now no glucose sensor has been available that can be used by diabetic patients in daily life conditions. Also one type of glucose sensor, a glucose electrode, recently received approval by the Food and Drug Administration (USA) and is commercially available. Other glucose sensors employing the transdermal, microdialysis or open tissue microperfusion technique are currently under clinical development and may also become available in the near future. The types of glucose sensors referred to so far are not truly non-invasive, but only minimally invasive. They measure glucose concentration in the interstitial fluid of the skin or the subcutis. Non-invasive optical glucose sensors are designed to monitor glucose changes in the skin by directing light through it. They measure the characteristics of the reflected light that are changed as the result of an interaction with glucose. However, none of the attempts with optical glucose sensors have resulted thus far in the development of a sensor that allows monitoring of glucose with sufficient accuracy and precision within the clinically relevant glucose range in daily life conditions. Nevertheless, more minimal-invasive glucose sensors systems will become available for practical use in the near future, whereas it is still uncertain if this can be said for any non-invasive glucose sensor.

Blood Glucose↗

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Short-term evaluation of an electro-chemical system (ExacTech) for blood glucose monitoring.

114 venous blood samples (plasma glucose ranging between 2.6 and 30.7 mmol/l) were measured by a new pen-sized glucose meter designed for blood glucose self-monitoring working with an electro-chemical method. Glucose readings of three pen-meters were compared with plasma glucose measurements obtained from a standard glucose-oxidase-method. Precision, accuracy and clinical relevance were determined by assessment of the agreement between the two methods and error grid analysis. The mean differences between the pen-meters' blood glucose readings and plasma glucose were -1.35, -1.43 and -1.56 mmol/l, with limits of agreement (+/- 2 SD) of 2.2 and -4.9, 2.1 and -5.0 and 2.0 and -5.1 mmol/l, respectively. The 57 samples in the clinically relevant range, i.e., with plasma glucose concentrations below 13 mmol/l showed mean differences of -0.04, -0.10, and -0.04 mmol/l, with limits of agreement between -1.08 and 1.00 mmol/l, respectively. Error grid analysis showed that 90.7, 95.4, and 91.9% of the respective pen-meter readings fell in the zone A, i.e., gave clinically accurate results, the remaining values fell in zone B. One pen-meter broke during the study and had to be replaced. The results confirm that this new device gives accurate and reproducible measurements--faultless technical function provided--and, compares favorably with the well-established reagent strips for blood glucose self-monitoring.

Biosensing Techniques↗

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Insulin analogues--not faster than U 40 regular human insulin?

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Aspartic Acid↗

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Near-normotension and near-normoglycemia in blind type I diabetic patients with overt diabetic nephropathy.

In patients with diabetic nephropathy, near-normalization of blood pressure (BP) and blood sugar may have a beneficial impact on changes in kidney function, but visually impaired patients may face difficulties when striving for optimal control of hypertension and hyperglycemia. In a prospective feasibility study, we followed a group of nine blind Type I (insulin-dependent) diabetic patients (mean age 30 +/- 4 years) with overt diabetic nephropathy and uncontrolled hypertension. All patients received intensified insulin therapy after a structured diabetes treatment and teaching program, and adapted their antihypertensive drug treatment to self-monitored BP values. At recruitment, HbA1c values were 5.8 +/- 0.6%, and remained stable at 6.3 +/- 1.7% after a mean observation period of 27 months. BP pressure decreased from 150 +/- 14/99 +/- 14 mmHg to 130 +/- 17/86 +/- 10 mmHg after 1 year, and to 140 +/- 14/92 +/- 9 mmHg at the last examination, (p less than 0.05). Serum creatinine and creatinine clearance remained stable over the observation period at 165 +/- 56 mumol/L and 0.8 +/- 0.4 ml/s/1.72m2 at recruitment, and 152 +/- 47 mumol/L and 1.0 +/- 0.5 ml/s/1.72m2 at the final examination. Proteinuria decreased from 3.2 to 1.4 g/24 h (p less than 0.05). No patient needed renal replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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Treatment of resistant schizophrenics with extreme high dosage fluphenazine hydrochloride.

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Adult↗

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Atrial natriuretic factor in various stages of diabetic nephropathy.

Plasma concentrations of atrial natriuretic factor (ANF) were measured by radioreceptor assay in 148 insulin-dependent Type I diabetic patients with different stages of diabetic nephropathy. In patients with overt or incipient diabetic nephropathy as well as in patients with glomerular hyperfiltration only, ANF concentrations were elevated when compared with non-nephropathic diabetic and normal subjects. No correlations between ANF and blood pressure, age, diabetes duration, or parameters of metabolic control were found. These findings may indicate a pathophysiologic role of ANF in the development and progression of diabetic nephropathy.

Adult↗

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Hypoglycemia and insulin analogues: is there a reduction in the incidence?

Rapid-acting insulin analogues were developed in answer to the need for a more appropriate time-action profile for prandial insulin substitution therapy. Improvements in at least one of three important endpoints needs to be demonstrated-metabolic control, hypoglycemic events, and/or quality of life-if there is to be a case for use of a new insulin preparation. This paper considers the data available on hypoglycemic events in the 24 controlled clinical trials (19 open, unblinded, and 5 double-blind) reported to date with rapid-acting insulin analogues (22 studies with insulin lispro). A significant reduction in the incidence of mild hypoglycemia was observed in 5 of 22 studies (22%). No change in frequency of severe hypoglycemic episodes was observed 10 of 12 studies (83%) reporting such events. A decrease in the frequency of nocturnal hypoglycemia has been reported in six studies; however, in the other 18 studies, no similar decrease in numbers were reported. There is no evidence for a reduction in patient awareness of hypoglycemia with rapid-acting insulin analogues. Even a slight reduction in hypoglycemic events would be welcomed by diabetic patients. However, rapid-acting insulins are only appropriate for use in patients using an intensive insulin regimen. Such patients are well motivated and well educated and will be able to adapt their insulin therapy to take account of the changes in the time-action profile of the rapid-acting insulin analogues. Thus, rapid-acting insulin analogues do not appear to have revolutionized insulin therapy, but appropriate use should result in benefits such as improved metabolic control for diabetic patients.

Blood Glucose↗

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Life expectancy in Germany: possible reasons for the increasing gap between East and West Germany.

The current life expectancy of East and West Germans is different. After the late 1980s, life expectancy at birth in both regions, which was comparable in the early 1950s, became almost three years lower in East Germany. Life-table calculations of German birth cohorts since 1900 revealed that a difference between the groups in cardiovascular disease prevalence was associated with the difference in life expectancy. Whereas migration, environmental pollution, and health-care differences accounted for only a small part of the gap, evidence emerged that lifestyle and social patterns may have caused the less favourable trend in cardiovascular disease. The life-expectancy curve has flattened in East Germany while continuously increasing in West Germany. During the 1960s and 1970s, such opposite trends were due to steeply increasing blood-pressure and cholesterol levels in East Germany and more favourable social development in West Germany--a better average social class (higher educational levels and a lower proportion of working-class individuals), a higher gross national product, and a higher proportion of GNP spent on health. Both the cardiovascular-risk-factor trends and the social gradient have contributed to the gap between the populations of East and West Germany in life expectancy.

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Nutritional behaviour differences in Germany.

East- and west-German health inequalities that emerged in the 1960s and 1970s centered not only on cardiovascular mortality but also on lifestyle-dependent risk factors, thus a question that should be addressed is whether different dietary behaviours existed in the two sections of Germany. To answer this question, we examined two random-sample population surveys--MONICA in the east and VERA in the west--that were carried out during the late 1980s. In the eastern section of Germany, the consumption of milk, vegetable oil and fat, fresh vegetables and tropical fruits was much lower than that in the west, whereas the intake of sausages and butter was much higher. Consequently, the calorie intake in the east was higher for fat and lower for carbohydrates before reunification. Changes in dietary habits were anticipated in East Germany after reunification because of important changes in the food supply. Analysis of an east-German dietary survey that was carried out after the wall came down revealed that the improved food supply to the east, with more choices for planning a healthy diet, led to a favourable development in both macro- and micro-nutrient intake, more carbohydrates, vitamins, calcium, and potassium were consumed.

Adult↗

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Social gradient of CVD risk in Germany before/after unification.

A social gradient of cardiovascular risk has been found in several European countries, including the former East and West Germany. Have any changes have occurred in Germany, particularly in the east, since the wall came down? We analyzed the results of three compatible, population-based, interview-and-examination health surveys that were performed in both parts of Germany between 1984 and 1992. Total years of education was the social indicator. Systolic/diastolic blood pressure, body mass index, prevalence of hypertension, obesity, and cigarette smoking showed a social gradient in favor of higher social class groups; the social gradient for total cholesterol and hyper-cholesterolemia in men was less clear. Despite a much higher risk-factor profile in the east, neither a difference between the social gradients of the former East and West Germany nor a clear trend after the wall came down were found. In both areas, the social gradient clearly increased only for women smokers. Overall, we found very little evidence to support the idea that the ferocity of socioeconomic changes in the east had already led to a higher gradient of cardiovascular risk in 1991/1992 relative to that in the western part of the German population.

Adult↗