[Hyperglycemia in critically ill]. / Therapie der Hyperglykämie bei erwachsenen, kritisch kranken PatientInnen (Update 2023).

In critical illness hyperglycemia is associated with increased mortality. Based on the currently available evidence, an intravenous insulin therapy should be initiated when blood glucose is above 180 mg/dl. After initiation of insulin therapy blood glucose should be maintained between 140 and 180 mg/dl.

A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes (AWARD-8).

AIMS: To evaluate the safety and efficacy of once-weekly dulaglutide 1.5 mg, a long-acting glucagon-like peptide-1 receptor agonist, compared with placebo in patients with type 2 diabetes (T2D) on glimepiride monotherapy. METHODS: This phase III, randomized (4 : 1; dulaglutide:placebo), double-blind, placebo-controlled, 24-week study compared the safety and efficacy of once-weekly dulaglutide 1.5 mg with placebo in sulphonylurea-treated (≥half-maximal dose, stable ≥3 months) patients (N = 300) with T2D and inadequate glycaemic control [glycated haemoglobin (HbA1c) ≥7.5 and ≤9.5% (≥58 mmol/mol and ≤80 mmol/mol)]. Analysis was carried out according to intention-to-treat. RESULTS: At baseline, the mean participant age was 58 years; mean HbA1c was 8.4% (68 mmol/mol) and mean weight was 85.5 kg. Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between-group HbA1c difference of -1.3% [95% confidence interval (CI) -1.6, -1.0] or -14 mmol/mol (95% CI -17, -11); p < 0.001. A greater proportion of participants in the dulaglutide group reached an HbA1c level of <7.0% (53 mmol/mol) compared with placebo (55.3% vs 18.9%; p < 0.001). Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo (between-group difference -1.86 mmol/l (95% CI -2.58, -1.14) or -33.54 mg/dl (95% CI -46.55, -20.53); p < 0.001. Weight was decreased significantly from baseline in the dulaglutide group (p < 0.001); the between-group difference was not significant. The most common treatment-emergent adverse events for dulaglutide 1.5 mg were gastrointestinal: nausea (10.5%), diarrhoea (8.4%) and eructation (5.9%). Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo (2.37 and 0.07 events/participant/year, respectively; p = 0.025). No severe hypoglycaemia was reported. CONCLUSIONS: Once-weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy.

Self-reported non-severe hypoglycaemic events in Europe.

AIMS: Hypoglycaemia presents a barrier to optimum diabetes management but data are limited on the frequency of hypoglycaemia incidents outside of clinical trials. The present study investigated the rates of self-reported non-severe hypoglycaemic events, hypoglycaemia awareness and physician discussion of events in people with Type 1 diabetes mellitus or insulin-treated Type 2 diabetes mellitus. METHODS: People in seven European countries aged >15 years with Type 1 diabetes or insulin-treated Type 2 diabetes (basal-only, basal-bolus and other insulin regimens) were recruited via consumer panels, nurses, telephone recruitment and family referrals. Respondents completed four online questionnaires. The first questionnaire collected background information on demographics and hypoglycaemia-related behaviour, whilst all four questionnaires collected data on non-severe hypoglycaemic events in the preceding 7 days. RESULTS: Analysis was based on 11 440 respondent-weeks from 3827 respondents. All participants completed the first questionnaire and 57% completed all four. The mean number of events/respondent-week was 1.8 (Type 1 diabetes) and 0.4-0.7 (Type 2 diabetes, with different insulin treatments) corresponding to annual event rates of 94 and 21-36, respectively. A total of 63% of respondents with Type 1 diabetes and 49-64% of respondents with Type 2 diabetes, treated with different insulin regimens, who experienced hypoglycaemic events, reported impaired hypoglycaemia awareness or unawareness. A high proportion of respondents rarely or never informed their general practitioner/specialist about hypoglycaemia: 65% (Type 1 diabetes) and 50-59% (Type 2 diabetes). Overall, 16% of respondents with Type 1 diabetes and 26% of respondents with Type 2 diabetes reported not being asked about hypoglycaemia during routine appointments. CONCLUSION: Non-severe hypoglycaemic events are common amongst people with Type 1 diabetes and insulin-treated Type 2 diabetes in real-world settings. Many rarely or never inform their general practitioner/specialist about their hypoglycaemia and the real burden of hypoglycaemia may be underestimated.

A two-step screening algorithm including fasting plasma glucose measurement and a risk estimation model is an accurate strategy for detecting gestational diabetes mellitus.

AIMS/HYPOTHESIS: It is currently not clear how to construct a time- and cost-effective screening strategy for gestational diabetes mellitus (GDM). Thus, we elaborated a simple screening algorithm combining (1) fasting plasma glucose (FPG) measurement; and (2) a multivariable risk estimation model focused on individuals with normal FPG levels to decide if a further OGTT is indicated. METHODS: A total of 1,336 women were prospectively screened for several risk factors for GDM within a multicentre study conducted in Austria. Of 714 women (53.4%) who developed GDM using recent diagnostic guidelines, 461 were sufficiently screened with FPG. A risk prediction score was finally developed using data from the remaining 253 women with GDM and 622 healthy women. The screening algorithm was validated with a further 258 pregnant women. RESULTS: A risk estimation model including history of GDM, glycosuria, family history of diabetes, age, preconception dyslipidaemia and ethnic origin, in addition to FPG, was accurate for detecting GDM in participants with normal FPG. Including an FPG pretest, the receiver operating characteristic AUC of the screening algorithm was 0.90 (95% CI 0.88, 0.91). A cut-off value of 0.20 was able to differentiate between low and intermediate risk for GDM with a high sensitivity. Comparable results were seen with the validation cohort. Moreover, we demonstrated an independent association between values derived from the risk estimation and macrosomia in offspring (OR 3.03, 95% CI 1.79, 5.19, p < 0.001). CONCLUSIONS/INTERPRETATION: This study demonstrates a new concept for accurate but cheap GDM screening. This approach should be further evaluated in different populations to ensure an optimised diagnostic algorithm.

The impact of risk factors and more stringent diagnostic criteria of gestational diabetes on outcomes in central European women.

OBJECTIVES: In the face of the ongoing discussion on the criteria for the diagnosis of gestational diabetes (GDM), we aimed to examine whether the criteria of the Fourth International Workshop Conference of GDM (WC) select women and children at risk better than the World Health Organization (WHO) criteria. DESIGN AND SETTING: This was a prospective longitudinal open study in five tertiary care centers in Austria. PATIENTS AND OUTCOME MEASURES: The impact of risk factors, different thresholds (WC vs. WHO), and numbers of abnormal glucose values (WC) during the 2-h, 75-g oral glucose tolerance test on fetal/neonatal complications and maternal postpartum glucose tolerance was studied in 1466 pregnant women. Women were treated if at least one value according to the WC (GDM-WC1) was met or exceeded. RESULTS: Forty-six percent of all women had GDM-WC1, whereas 29% had GDM-WHO, and 21% of all women had two or three abnormal values according to WC criteria (GDM-WC2). Eighty-five percent of the GDM-WHO were also identified by GDM-WC1. Previous GDM [odds ratio (OR) 2.9], glucosuria (OR 2.4), preconceptual overweight/obesity (OR 2.3), age 30 yr or older (OR 1.9), and large-for-gestational age (LGA) fetus (OR 1.8) were the best independent predictors of the occurrence of GDM. Previous GDM (OR 4.4) and overweight/obesity (OR 4.0) also independently predicted diabetes postpartum. GDM-WC1 had a higher rate of obstetrical complications (LGA neonates, neonatal hypoglycemia, cesarean sections; P < 0.001) and impaired postpartum glucose tolerance (P < 0.0001) than GDM-WHO. CONCLUSION: These results suggest the use of more stringent WC criteria for the diagnosis of GDM with the initiation of therapy in case of one fasting or stimulated abnormal glucose value because these criteria detected more LGA neonates with hypoglycemia and mothers with impaired postpartum glucose metabolism than the WHO criteria.

The SREBF-1 locus is associated with type 2 diabetes and plasma adiponectin levels in a middle-aged Austrian population.

CONTEXT: The sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor involved in the regulation of lipid and glucose metabolism and has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM). OBJECTIVE: We aimed to confirm associations of the SREBF-1 gene with T2DM in an Austrian population and to study possible associations with diabetes-related quantitative traits. DESIGN, SETTINGS AND PARTICIPANTS: We genotyped a diabetic cohort (n=446) along with a control group (n=1524) for a common C/G variation that is located in exon 18c (rs2297508) and has been associated with obesity and T2DM in French populations. MAIN OUTCOME MEASURES: Body mass index (BMI), indices of insulin sensitivity and beta-cell function, plasma adiponectin, T2DM and single-nucleotide polymorphism rs2297508. RESULTS: Genotype distributions associated with rs2297508 differed by T2DM status (P=0.0045), but not by BMI. The variant G allele was associated with a modest, but significant, increase in the prevalence of T2DM after adjustment for age, sex and BMI (G/G: odds ratios (OR) (95% confidence intervals)=1.45 (0.99-2.11) and G/C: OR=1.37 (1.04-1.81)). In a cross-sectional population of non-diabetic subjects, associations of rs2297508 genotypes with plasma adiponectin levels adjusted for age, sex and BMI (P=0.0017) were observed in that the risk G/G genotype displayed the lowest adiponectin levels. CONCLUSIONS: We observed associations of rs2297508 with T2DM prevalence and plasma adiponectin. SREBP-1c has been implicated in the regulation of adiponectin gene expression. Our results therefore raise the possibility that sequence variations at the SREBF-1 gene locus might contribute to T2DM risk, at least in part, by altering circulating adiponectin levels.

Cholesteryl ester transfer protein TaqIB polymorphism and its relation to parameters of the insulin resistance syndrome in an Austrian cohort.

The cholesteryl ester transfer protein (CETP) is responsible for the exchange of triglycerides and cholesteryl esters between lipoprotein particles leading to an increased hepatic clearance of HDL-cholesteryl esters. A high CETP activity reduces serum HDL levels, whereas persons without CETP activity have high HDL levels. We investigated the association of the TaqIB CETP polymorphism and various parameters of the insulin resistance syndrome in a cross sectional population based study. We included 1029 persons without known cardiovascular disease or diabetes mellitus consecutively enrolled in our SAPHIR program (Salzburg Atherosclerosis Prevention program in persons with a High Infarction Risk). Numerous clinical and laboratory data were accomplished. Insulin sensitivity was measured by a short insulin tolerance test. The TaqIB CETP polymorphism was determined by PCR, TaqI restriction and electrophoresis. 35.2% were homozygous for the prevalence (B1B1), 46.7% were heterozygous (B1B2), and 18.1% homozygous for the absence (B2B2) of the restriction site. HDL cholesterol and apolipoprotein A1 were lower and small dense low-density lipoproteins (sdLDL) higher in B1B1 compared to B2B1 and B2B2 persons. In women, we found a significant interaction effect between CETP genotype and adiposity for HDL cholesterol. B1B1 women with a BMI and a waist circumference above the median had 9.7 mg/dl lower HDL than B1B2 and 9.1 mg/dl lower HDL than B2B2 women (P < 0.001). In men, no interaction effect but a marked genotype to HDL correlation was found. There was a high CETP effect on sdLDL detected in men (P = 0.001). B1B1 men had sdLDL in 36%, B1B2 in 24.6%, and B2B2 in only 14.5%. Men with adiposity and insulin resistance had twice as many sdLDL as insulin sensitive men. We found a significant sex specific effect of the TaqIB CETP polymorphism on the insulin resistance parameters HDL-cholesterol and sdLDL in an Austrian population based study.

Antibodies to heat-shock protein 65 and neopterin levels in patients with type 1 diabetes mellitus.

Antibodies to heat shock protein (hsp) are strongly associated with atherosclerotic cardiovascular disease in the non-diabetic population as well as in patients with type 2 diabetes mellitus. In type 1 diabetes increased antibody titers to hsp were found to be a symptom of the autoimmune disease leading to beta-cell damage. We asked whether hsp antibody titers are related to metabolic control and late complications in type 1 diabetic patients. Serum neopterin, also an indicator of chronic inflammation, was also evaluated. The hsp65 antibody titer was determined in 138 patients with type 1 diabetes, 47 women and 91 men, aged 35.5 +/- 12 years with a mean diabetes duration of 16.6 +/- 10.5 years. A history of diabetic late complications and cardiovascular disease was taken. A fundoscopy and a neurological examination were performed, nephropathy was assessed by measurement of the urinary albumin excretion rate. For the measurement of the hsp antibody titer an enzyme-linked immunosorbent assay (ELISA) was applied, for neopterin a radio-immuno assay (RIA) was used. The hsp65 antibody titer was found to be positively related to the patients' age (r = 0.237; p < 0.035). Patients with retinopathy revealed significantly higher hsp65 antibody titers (307.2 +/- 38.6) than those without retinopathy (150.0 +/- 18.5;p < 0.003). No correlation was found between hsp antibody titer and metabolic control. Serum neopterin levels revealed a trend towards a positive relationship with diabetes duration (r = 0.205; p < 0.0539) and a significant correlation with serum cholesterol levels (r = 0.436; p < 0.001), but not with HbA1 c values. Our data add further information to the role of inflammatory markers in the development of diabetic microangiopathy.

[Risk status of screened population based on elevated serum cholesterol values]. / Risikostatus der untersuchten Population aufgrund der erhobenen Serumcholesterinwerte.

The mean value of serum total cholesterol was 208 +/- 42 mg/dl for the study population. Sixty-five percent of investigated subjects had elevated cholesterol levels > 200 mg/dl. The percentage of subjects with low to moderate elevated cholesterol levels between 200-250 mg/dl was 40%, and 2% had a cholesterol higher than 300 mg/dl. Grouping the cholesterol levels by age and sex resulted in a high percentage of subjects with serum cholesterol > 200 mg/dl for the cardiovascular high-risk age group of 45-65 years old men and 55-75 years old women. Remarkably high was this percentage for women in this age-group; 71% had a cholesterol level > 200 mg/dl. In 59% of investigated women and 52% of men cholesterol should be lowered.

Candida attachment to oral epithelium.

Inflamed oral mucosa biopsies from patients with thrush and high candidal density were observed in a transmission electron microscope (TEM) using ultra-histochemical staining with ruthenium red for glycocalyx visualization. Fimbriae comprising the glycocalyx and enabling yeast adhesion to epithelial cells were clearly visualized by ruthenium red. All internalized portions of the yeast walls were devoid of glycocalyx, indicating that the growing tips of the hyphae mechanically penetrated the host cells. The attachment of Candida occurred in two ways: by fimbria-mediated adhesion enabling colonization of the epithelial surface, and by invasion of the superficial epithelial cells via hyphae. As the interaction between adhesin receptors and adhesins stimulates the production of proinflammatory cytokines, Candida adhesion itself is assumed to induce mucosal inflammation.

High-fructose diet preserves beta-cell mass and prevents diabetes in nonobese diabetic mice: A potential role for increased insulin receptor substrate-2 expression.

We demonstrate that a high-fructose diet reduces the incidence of diabetes in nonobese diabetic (NOD) mice (31.2% v 57.1% on regular chow (RC); P =.009). In a second cohort of mice, we evaluated potential mechanisms for the protective effect of the high-fructose (HF) diet and whether the metabolic changes are strain-specific. Sixty NOD and 60 Balb/c mice were randomized at weaning into HF- and RC-fed groups (30 mice each) and followed for 28 weeks. Glucose tolerance testing demonstrated improved glucose tolerance in HF diet groups (P =.001 in Balb/c; P =.04 in NOD mice at 6 months). beta-cell mass was preserved in NOD mice on the HF diet, but remained unchanged in Balb/c mice. In NOD mice, hepatic insulin receptor substrate (IRS)-2 protein expression increased by 2-fold (P =.01 for 2 v 6 months) in HF-fed mice and was 53% +/- 15% higher (P =.01) in the HF diet versus RC groups at 6 months of age. IRS-2 expression was also increased in skeletal muscle of NOD mice and in both liver and muscle of Balb/c mice. Our data suggest that a HF diet improves glucose tolerance in both NOD and Balb/c mice. The improved glucose tolerance may be related to increased IRS-2 expression and, in NOD mice, preservation of beta-cell mass.

Immunohistochemical assessment of an asymptomatic glucagonoma in a patient with hypergastrinemia and marked antral angiodysplasia.

A 58-year-old patient had been treated for recurrent gastritis. Numerous gastroscopies indicated hemorrhagic gastritis combined with increasingly severe anemia. The patient was admitted with a hemoglobin of 4.4 g/dL. Gastroscopy showed marked antral angiodysplasia. Serum samples for gastrin were taken and found to be elevated (170-250 U/mL). The search for a gastrin-producing tumor with abdominal ultrasound, computed tomography, octreotide scan, and secretin test was negative, but angiography detected a pancreas tumor with a 2-cm diameter. Partial pancreatectomy and partial gastrectomy were performed. Immunohistochemical examination of the tumor did not show a gastrinoma but did show glucagon-reactive tissue. Further tumors or elevated plasma hormone levels were not detected, and a multiple endocrine neoplasia type I syndrome could be excluded. We thus found antral angiodysplasia with hypergastrinemia leading to detection of a glucagonoma diagnosed by immunohistochemistry. After more than 4 years of follow-up, the patient is without any symptoms or signs of relapse or secondary hormone syndrome.

Association of HELLP syndrome with autoimmune antibodies and glucose intolerance.

OBJECTIVE: HELLP syndrome is a severe form of preeclampsia, characterized by hemolysis (H), elevated liver enzymes (EL), and low platelets (LP), whose pathogenesis is unclear. Autoimmunity is thought to play an important role. After the observation of development of type 1 diabetes in a patient with HELLP syndrome, we assumed a possible disease association based on autoimmune reactions. RESEARCH DESIGN AND METHODS: We examined 70 women with HELLP syndrome for the presence of autoimmune markers and glucose intolerance. Free thyroxine, triiodothyronine, thyroid-stimulating hormone, anti-thyroglobulin antibodies, thyroperoxidase antibodies, thyrotropin receptor antibodies, antinuclear antibodies (ANAs) and anti-DNA, islet cell antibodies, GADA, an oral glucose tolerance test, and HbA1c were determined postpartum. Patients with positive autoimmune markers or glucose intolerance were prospectively followed and repeated testing was performed. There were 60 women with a normal course of pregnancy matched for age, BMI, and number of pregnancies, which served as a control group. RESULTS: From the HELLP patients, 22 (31%) compared with only 6 (10%) control subjects had autoimmune antibodies (P < 0.01). There were 16 HELLP patients (23%) who exhibited only 1 kind of autoantibody (5 ANA, 9 thyroid antibodies, and 2 GADA), whereas in 6 HELLP patients (8.5%) 2 different antibodies were found. In all but 4 patients of the study group, these antibodies disappeared during 3 +/- 1.5 years of follow-up. Glucose intolerance was detected in 22 (31%) of the HELLP patients, 17 of them had impaired glucose tolerance (IGT), and 5 had diabetes, whereas only 4 subjects (6.5%) with IGT at postpartum were found in the control group (P < 0.01). During the follow-up, 2 HELLP patients were still diabetic and another 2 HELLP patients (1 GADA positive) had IGT versus 1 control subject. CONCLUSIONS: Our data give evidence that HELLP syndrome is associated with various autoimmune antibodies and glucose intolerance. Because glucose intolerance and/or autoimmune markers persisted during long-term follow-up in 6 patients with HELLP syndrome versus 1 in the control group, it may become advisable to reexamine patients with HELLP syndrome for detection of diabetes and autoimmune disorders.

Prospective evaluation of urinary N-acetyl-beta-D-glucosaminidase with respect to macrovascular disease in elderly type 2 diabetic patients.

OBJECTIVE: To analyze prospectively the importance of urinary N-acetyl-beta-D-glucosaminidase (NAG), a marker for renal tubular function, in comparison with urinary albumin excretion (UAE), a marker for glomerular renal function, with respect to macrovascular disease in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed 124 patients over a mean period of 7.0 +/- 0.5 years. At baseline, urinary NAG, UAE, age, diabetes duration, sex, blood pressure, lipids, and serum creatinine were determined. Also, history of myocardial infarction (MI), stroke, severe peripheral vascular disease (PVD), antidiabetic and concomitant medication, and smoking habits were recorded. After 7 years, patients were reevaluated, and a multivariate logistic regression analysis was used to test risk factors for significance in order to predict macrovascular disease. Subgroups of patients were analyzed with respect to severe macrovascular disease, with a separate analysis for surviving patients. RESULTS: Compared with known cardiovascular risk factors such as microalbuminuria and total cholesterol, urinary NAG was similarly associated with cardiovascular disease for the total cohort (P < 0.05). Analyzing the subgroup of 65 patients still alive after follow-up care, urinary NAG and UAE were significantly elevated at baseline and at the time of follow-up care in patients with MI and PVD, but not in those with stroke (P < 0.01). There was a positive predictive trend of NAG excretion for the development of MI and PVD in our patients (P = 0.07). CONCLUSIONS: Urinary NAG proved comparable to UAE when analyzed with respect to preexistence and development of severe macrovascular disease. It needs to be determined by further studies if urinary NAG will be of value to serve as an adjunct marker to UAE in type 2 diabetic patients.

Newer portable glucose meters--analytical improvement compared with previous generation devices?

BACKGROUND: Newer glucose meters are easier to use, but direct comparisons with older instruments are lacking. We wished to compare analytical performances of four new and four previous generation meters. METHODS: On average, 248 glucose measurements were performed with two of each brand of meter on capillary blood samples from diabetic patients attending our outpatient clinic. Two to three different lots of strips were used. All measurements were performed by one experienced technician, using blood from the same sample for the meters and the comparison method (Beckman Analyzer 2). Results were evaluated by analysis of clinical relevance using the percentage of values within a maximum deviation of 5% from the reference value, by the method of residuals, by error grid analysis, and by the CVs for measurements in series. RESULTS: Altogether, 1987 blood glucose values were obtained with meters compared with the reference values. By error grid analysis, the newer devices gave more accurate results without significant differences within the group (zone A, 98-98.5%). Except for the One Touch II (zone A, 98.5%), the other older devices were less exact (zone A, 87-92.5%), which was also true for all other evaluation procedures. CONCLUSIONS: New generation blood glucose meters are not only smaller and more aesthetically appealing but are more accurate compared with previous generation devices except the One Touch II. The performance of the newer meters improved but did not meet the goals of the latest American Diabetes Association recommendations in the hands of an experienced operator.

Glycaemic disorders in denture stomatitis.

The prevalence of glycaemic disorders was investigated in native Upper-Austrians with Candida-associated denture stomatitis. All patients with previously unknown diabetes mellitus were subjected to an oral glucose tolerance test (OGTT) and as a result diabetes was diagnosed in 13% of the patients over 50 years of age. Thirty-five percent of all inspected patients over 50 years of age with denture stomatitis had type 2 diabetes mellitus and 36% had impaired glucose tolerance (IGT). The correlation between Candida-associated denture stomatitis and diabetes mellitus indicates a means for the early diagnosis of diabetes. Hyperglycaemia could not be a predisposition to denture stomatitis, since all patients with denture stomatitis in the age-bracket 26-50 years were without diabetes and only very few of the older patients with diabetes were obese. The correlation between Candica-associated denture stomatitis and type 2 diabetes mellitus could be traced back to a reduced resistance to Candida that preceded the diabetes.

[Blood glucose self-monitoring in intensified insulin therapy: acceptance of frequent measurements and effect on quality of diabetic control]. / Blutzucker-Selbstkontrolle unter intensivierter Insulintherapie: Akzeptanz häufiger Kontrollen und Auswirkung auf die Qualität der Diabeteseinstellung.

In intensive insulin therapy frequent measurements of blood glucose are necessary for daily insulin adjustments. The aim of our study was to determine acceptance of frequent blood glucose measurements and its relation to quality of glycemic control over a period of 5 years. We report on 57 unselected patients with type 1 diabetes mellitus, who were at least half a year under intensive insulin therapy when entering the study. Mean age was 34 +/- 9, diabetes duration 18 +/- 8 years. The number of daily blood glucose measurements, HbA1c, body mass index, daily insulin dose, routine laboratory values, number of severe hypoglycemic reactions and frequency of retinopathy, nephropathy and neuropathy were determined for year 1 and 5. We found an increase in daily blood glucose measurements from 2.5 to 4.5 per day (year 1 resp. year 5). The frequency of blood glucose measurements at the begin of our study respectively after 5 years was: < or = 2.0/day in 51% vs. 12%, > 2.0 but < 4.0/day in 20% vs. 21% and > or = 4.0/day in 29% vs. 67% of patients. HbA1c decreased from 7.3 +/- 1.2 to 6.4 +/- 1.1% after 5 years (p < 0.001). A comparison of subgroups of patients showed that frequency of blood glucose measurement is not the only cause for this improvement, but adequate education of diabetic patients seems to be most important. Retinopathy and neuropathy increased despite better diabetic control, 2 patients developed microalbuminuria, all other data determined at study entry remained unchanged after 5 years. We conclude that frequent daily blood glucose measurements were accepted by the majority of our patients over a long period of time. Mean blood glucose determined by HbA1c improved under intensive insulin therapy. In our study group with low HbA1c values at baseline this effect was only partly related to the frequency of daily blood glucose measurements.