[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.

[Antihyperglycemic Treatment Guidelines for diabetes mellitus type 2]. / Antihyperglykämische Therapie bei Diabetes mellitus Typ 2. Grundsatz Statement.

Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets in regard of optimal therapeutic efficacy and high therapeutic safety is of great importance. In this guideline we present the best and most current evidence-based clinical practice data for healthcare professionals.

Association of low-grade inflammation with nephropathy in type 2 diabetic patients: role of elevated CRP-levels and 2 different gene-polymorphisms of proinflammatory cytokines.

BACKGROUND: Chronic inflammatory processes are thought to play a key role in the development of micro- and macrovascular complications in type 2 diabetes mellitus. An association between low -grade inflammation and type 2 diabetes has been described in some studies. We assayed the association of two frequent polymorphisms in proinflammatory cytokines: the interleukin 6 G(-174)C promoter polymorphism [IL-6G(-174)C], the exon 2 interleukin receptor antagonist insertion deletion polymorphism [IL1RA]) and serum CRP levels with the prevalence of diabetic nephropathy in patients suffering from type 2 diabetes mellitus. SUBJECTS AND METHODS: A total of 141 patients with type 2 diabetes mellitus, with and without diabetic nephropathy was genotyped for the above mentioned polymorphisms: 66 with normoalbuminuria, 31 with microalbuminuria and 44 with macroalbuminuria. CRP levels were analysed by a high sensitivity - immunnephelometric assay. RESULTS: While a significant association be-tween macroalbuminuria and CRP could be observed (p<0,015), no associations were found between IL-6G(-174)C or IL1RA genotype and any stage of nephropathy. CRP-levels were similar in the 3 different IL-6G(-174)C genotypes as well as in the 2 IL1RA genotypes. CONCLUSIONS: In type 2 diabetic subjects elevated CRP levels are associated with an increased prevalence of albuminuria. The two investigated proinflammatory polymorphisms do not seem to contribute to initiation of nephropathy in type 2 diabetic patients but we cannot exclude effects of these polymorphisms on course of nephropathy.

Improvement of glucose tolerance in type 2 diabetic patients: traditional vs. modern insulin regimens (results from the Austrian Biaspart Study).

OBJECTIVE: Major advantages of modern insulin regimens containing premixed insulin analogues in comparison to traditional insulin regimens have not been evaluated yet. The aim of the present study was to investigate whether meal-related (breakfast, lunch, dinner) application of biphasic insulin aspart 30 (BIAsp 30) provides better glycaemic control than administration of biphasic human insulin 30 (BHI 30) twice per day. RESEARCH DESIGN AND METHODS: In a multi-centre, randomized, open-label parallel trial, a total of 177 patients with type 2 diabetes mellitus were exposed to the two different insulin regimens described above over a study period of 24 weeks. HbA1c and glycemic exposure parameters were measured at predefined intervals. RESULTS: The mean difference between treatment groups in HbA1c after 24 weeks of treatment was 0.08% (p = 0.6419). Analysing the 7-point blood-glucose (BG) profiles, significant differences in BG levels were observed after lunch (156 vs. 176 mg/dl, p = 0.0289), before dinner (142 vs. 166 mg/dl p = 0.006) and after dinner (154 vs. 182 mg/dl p = 0.002) in favour of BIAsp 30 insulin. Prandial BG increment was lower in the BIAsp 30 group at breakfast (p = 0.057) and lunch (p < 0.0005). No difference was found regarding safety parameters in the two treatment groups. CONCLUSIONS: This study demonstrates that meal-related BIAsp 30-insulin maintains postprandial BG control more effectively than traditional BHI 30 insulin twice per day in type 2 diabetic patients.

The value of the Rydel-Seiffer tuning fork as a predictor of diabetic polyneuropathy compared with a neurothesiometer.

AIMS: The aim of the study was to investigate the predictive value of the Rydel-Seiffer tuning fork for detecting diabetic neuropathy and to compare it with an electronic neurothesiometer. METHODS: In 2022 consecutive diabetic subjects, peripheral polyneuropathy was diagnosed by vibration perception threshold (VPT) at the tip of both great toes using a 128-Hz tuning fork and a neurothesiometer, by simple bedside tests and by the presence of neuropathic symptoms. These evaluations were further combined to diagnose peripheral nerve dysfunction (abnormal bedside tests) and symptomatic neuropathy. VPT was also measured in 175 non-diabetic control subjects to define normal values. RESULTS: VPT was normal in 1917 subjects and abnormal in 105 (5.2%) patients when measured by the tuning fork. Patients with an abnormal vibration test were significantly (P < 0.0001) older than subjects with a normal vibration sense, while diabetes duration and HbA(1c) of the former were also significantly elevated. The same was true for the percentages of an abnormal 10-g monofilament test (66.7% vs. 7.2%, P < 0.0001) and a missing Achilles' tendon reflex (68.6% vs. 24.8%, P < 0.0001). Finally, the VPT measured by the neurothesiometer was 2.5 times higher in patients with an abnormal tuning fork test (32.0 +/- 9.8 vs. 12.5 +/- 6.4 V, P < 0.0001). The plot of the difference of both methods against their mean yielded a good agreement of the two VPT measurements, and the tuning fork had a high sensitivity and positive predictive value for the diagnosis of abnormal bedside tests and for symptomatic neuropathy. CONCLUSION: The tuning fork reliably detected peripheral neuropathy in comparison with the neurothesiometer. A tuning fork is a useful screening test for diabetic neuropathy.

Trends in hypertension management in Type I diabetes across Europe, 1989/1990 - 1997/1999.

AIMS/HYPOTHESIS: Our aim was to examine the change in the management of hypertension in patients with Type I (insulin-dependent) diabetes mellitus in Europe, between 1989-1990 and 1997-1999. METHODS: Seven-year changes in hypertension treatment and control (defined as blood pressure <130/85 mmHg) were examined in a large sample of Type I diabetic patients recruited from 26 centres involved in the EURODIAB Prospective Complications Study. Hypertension was defined as a systolic and/or diastolic blood pressure greater than 140 and/or 90 mmHg respectively, and/or use of blood pressure lowering drugs. RESULTS: Of 1866 Type I diabetic patients, 412 had hypertension at baseline and 631 at follow-up. A greater proportion of hypertensive patients were treated at follow-up (69% vs 40%, p<0.0001), which persisted after adjustment for age or centre. Of those who were treated, a modest increase in the proportion of those controlled for hypertension was found (41% vs 32%, p=0.048), which disappeared after adjustment for age. Among hypertensive patients with albuminuria, the proportions treated also increased, from 35% to 76% ( p<0.0001) in microalbuminuric and 64% to 95% ( p<0.0001) in macroalbuminuric patients. Control of hypertension in albuminuric patients did not change significantly and was below 50%. The use of more than one anti-hypertensive drug increased over a 7-year period, from 19% to 33% ( p<0.0001), and a marked increase was shown in the proportion of those taking an ACE inhibitor (from 57% to 82%, p<0.0001). CONCLUSION/INTERPRETATION: The management of hypertension in Type I diabetic patients across Europe has improved over a 7-year follow-up period. Optimal levels of blood pressure treatment and optimal levels of control have not yet been achieved.

Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human.

Validated analytical methods (HPLC, CE and GC-MS) for determining the amount of andrographolide (AND) in the blood plasma of rats and human volunteers following the oral administration of Andrographis paniculata extract (APE) and Andrographis paniculata fixed combination Kan Jang tablets were developed and used for the pharmacokinetic study. Andrographolide was quickly and almost completely absorbed into the blood following the oral administration of APE at a dose of 20 mg/kg body wt. in rats. Its bio-availability, however, decreased four-fold when a 10-times-higher dose was used. Since a large part (55 %) of AND is bound to plasma proteins and only a limited amount can enter the cells, the pharmacokinetics of AND are described well by a one-compartment model. Renal excretion is not the main route for eliminating AND. It is most likely intensely and dose dependently metabolized. Following the oral administration of four Kan Jang tablets (a single therapeutic dose, equal to 20 mg of AND) to humans, maximum plasma levels of approximately 393 ng/ml (approx. 1.12 microM) were reached after 1.5-2 hours, as quantified using a UV diode-array detection method. Half-life and mean residence times were 6.6 and 10.0 hours, respectively. AND pharmacokinetics in humans are explained well by an open two-compartment model. The calculated steady state plasma concentration of AND for multiple doses of Kan Jang (after the normal therapeutic dose regimen, 3 x 4 tablets/day, about 1 mg AND/kg body wt./day) was approximately 660 ng/ml (approx. 1.9 microM), enough to reveal any anti-PAF effect, particularly after drug uptake when the concentration of AND in blood is about 1342 ng/ml (approx. 3.8 microM, while for anti-PAF effect EC50 - 5 microM).

ACE gene polymorphism and proliferative retinopathy in type 1 diabetes: results of a case-control study.

OBJECTIVE: To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. RESEARCH DESIGN AND METHODS: In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. RESULTS: The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. CONCLUSIONS: These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy

[Platelet aggregation inhibitors in diabetes mellitus]. / Aggregationshemmer bei Diabetes mellitus.

Major cardiovascular complications and ischemic events occur more frequently in diabetic than nondiabetic patients. Platelets of diabetic patients are found in a permanent prethrombotic state. Platelet activation and aggregation with resultant arterial thrombus formation, are the central mechanisms in the pathophysiology of acute coronary syndromes. Over the past two decades aspirin was the leading antithrombotic agent for reduction of thrombotic events and efficacy was proven in many studies. The main study concerning the aspirin question was the "Antiplatelet Trialist's Collaboration-Study", where a successful risk reduction for vascular events of 25%-34% was observed with daily dosis between 75 and 325 mg. In the last years some new, very effective drugs have been developed. Clopidogrel, a thienopyridine was studied in the CAPRIE trial and compared with aspirin. A small advantage could be proved for clopidogrel. The development of inhibitors of fibrinogen, binding to the platelet glykoprotein IIb/IIIa receptor has expanded the therapeutic spectrum for the treatment of thrombotic disorders. Especially in diabetic patients a significant benefit of these new drugs was demonstrated in various clinical indications. The newest results show the clear advantage of combining thrombolytic agents with the glycoprotein IIb/IIIa receptor antagonists in reperfusion after myocardial infarction. In conclusion the main message is, that diabetic patients do need antithrombotic therapy earlier than nondiabetic patients, that efficient drugs are available and that a primary prevention should be considered in this special patient group.

[Effect of nutrition on microalbuminuria in patients with type 1 diabetes: prospective data evaluation over 5 years]. / Einfluss der Ernährung auf die Mikroalbuminurie bei Patienten mit Typ 1 Diabetes: Prospektive Datenerhebung über einen Zeitraum von 5 Jahren.

The possible influence of dietary components on the progression or regression of microalbuminuria (MA) in type 1 diabetic patients was investigated prospectively over 5 years. The dietary intake of 47 patients with type 1 diabetes and MA (20-200 micrograms/min.), well instructed in diabetes management was observed in bimonthly intervals. Accuracy of 4-day diet protocols was verified by comparing the amount of documented protein intake with the measured nitrogen excretion. Non compliance was defined as deviation more than 30% between both values. These patients were eliminated from the study. Data from 37 patients with good compliance over a 5 year period have been used for multiple stepwise regression analysis. Taking into consideration Body mass index (BMI), blood pressure, HbA1c and time, MA was used as dependent variable, 16 dietary variables with a bivariate significance p < 0.05 as independent variables. The regression analysis (R2 = 0.589, p = 0.0015) showed clear associations between MA and the amount of salt intake (beta = 0.683, p < 0.002), saturated fatty acids (beta = 0.342, p = 0.029) and the amount of consumed mono- and disaccharides (beta = 0.479, p = 0.018). There was no significant association with the amount of protein intake (beta = 0.319, p = 0.152). Looking at the fatty acids in particular there were significant associations to MA with myristic acid, arachidonic acid and negatively with linoleic acid. Splitting the data in tertiles according to the amount of salt intake (I: < 6 g/d, II: 6-10 g/d, III: > 10 g/d) we could show in addition to the overall effect an intraindividual influence on the amount of MA (MA-means +/- SD: I: 45 +/- 56 micrograms/min., II: 61 +/- 59, III: 81 +/- 74, p < 0.001 between the groups). There were no significant differences between the groups in mean blood pressure, HbA1c and BMI.

Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus.

BACKGROUND: Retinopathy commonly occurs in people with type 1 diabetes. Strict glycaemic control can decrease development and progression of retinopathy only partially. Blood pressure is also a risk factor for microvascular complications. Antihypertensive therapy, especially with inhibitors of angiotensin-converting enzyme (ACE), can slow progression of nephropathy, but the effects on retinopathy have not been established. We investigated the effect of lisinopril on retinopathy in type 1 diabetes. METHODS: As part of a 2-year randomised double-blind placebo-controlled trial, we took retinal photographs at baseline and follow-up (24 months) in patients aged 20-59 in 15 European centres. Patients were not hypertensive, and were normoalbuminuric (85%) or microalbuminuric. Retinopathy was classified from photographs on a five-level scale (none to proliferative). FINDINGS: The proportion of patients with retinopathy at baseline was 65% (117) in the placebo group and 59% (103) in the lisinopril group (p = 0.2). Patients on lisinopril had significantly lower HbA1c at baseline than those on placebo (6.9% vs 7.3 p = 0.05). Retinopathy progressed by at least one level in 21 (13.2%) of 159 patients on lisinopril and 39 (23.4%) of 166 patients on placebo (odds ratio 0.50 [95% CI 0.28-0.89], p = 0.02). This 50% reduction was the same when adjusted for centre and glycaemic control (0.55 [0.30-1.03], p = 0.06). Lisinopril also decreased progression by two or more grades (0.27 [0.07-1.00], p = 0.05), and progression to proliferative retinopathy (0.18 [0.04-0.82], p = 0.03). Progression was not associated with albuminuric status at baseline. Treatment reduced retinopathy incidence (0.69 [0.30-1.59], p = 0.4). INTERPRETATION: Lisinopril may decrease retinopathy progression in non-hypertensive patients who have type 1 diabetes with little or no nephropathy. These findings need to be confirmed before changes to clinical practice can be advocated.

Evaluation of risk factors for the development of nephropathy in patients with IDDM: insertion/deletion angiotensin converting enzyme gene polymorphism, hypertension and metabolic control.

Diabetic nephropathy represents a major complication in patients with insulin-dependent diabetes mellitus (IDDM). Intervention trials using angiotensin-converting enzyme (ACE) inhibitors have pointed towards the important pathogenetic role of the renin-angiotensin system. Recently an insertion/ deletion (I/D) polymorphism for the gene encoding the ACE has been described, the deletion type being associated with higher plasma ACE levels. As the intrarenal renin-angiotensin system might also be activated in this setting, we determined the ACE genotype together with other risk factors for the development of diabetic nephropathy in 122 patients with IDDM from a single centre with (n = 63) and without (n = 59) nephropathy. Long-term glycaemic control was evaluated using mean HbA1c values from the last 10 years. The two patient group were comparable with regard to duration of diabetes and glycaemic control as assessed by current HbA1c values. However, mean long-term HbA1c values were significantly higher in patients with diabetic nephropathy as was systemic blood pressure. The DD genotype was more prevalent in patients with renal disease. In the subgroup of patients who had had diabetes for more than 20 years (n = 90), the DD genotype was even more frequent in patients with nephropathy, and blood pressure and long-term HbA1c values were also higher in patients with renal disease. Logistic regression analysis revealed long-term glycaemic control, blood pressure and the ACE genotype to be independent risk factors for the prevalence of diabetic nephropathy.

[Insulin-dependent diabetes mellitus:"EURODIAB IDDM Complications Study"--results from the Vienna center]. / Insulinabhängiger Diabetes mellitus: "EURODIAB IDDM complications study"--Ergebnisse des Wiener Zentrums.

The EURODIAB IDDM complications study is a multicenter clinical study for evaluation of the prevalence of microvascular, macrovascular and acute metabolic complications in randomly selected samples of insulin-dependent diabetic patients attending 31 European diabetes centers. A total of 3250 patients were studied (mean age: 32.7 +/- 10 years, mean duration of diabetes: 14.7 +/- 9.3 years) by standardized, validated methods. The third medical department of the Vienna-Lainz hospital participated from Austria. 122 patients, age: 34.9 +/- 9.9 years, duration of diabetes: 16 +/- 10 years were recruited from this center. There was a wide variation in the frequency of complications between the different European centres: Prevalence of diabetic retinopathy 25-60%; Vienna showed the lowest prevalence (25%). Metabolic control (HbA1c) ranged from 5.7-9.4%; Vienna shared the second place with two other centers (6.0%). Despite the very low HbA1c in the Viennese population, the frequency of severe hypoglycemic attacks was in the lower range, which is an extraordinary result in this study. Incipient diabetic renal disease, characterized by microalbuminuria varied in frequency between 15 and 33% (Vienna 23%). Important associations of raised blood pressure (frequency in all centers: 8-41%, Vienna: 29%) with renal disease and retinopathy have implications for the initiation of preventive measures. The data on diabetic complications obtained from the EURODIAB study permit a comparison between the different European centers and emphasize the need for implementation of the St. Vincent recommendations.

No effect of naloxone on ventilatory response to progressive hypercapnia in IDDM patients.

The ventilatory response to hyperoxic progressive hypercapnia was examined by comparing 3 test groups: 7 diabetic patients with AN, 8 diabetic patients without AN, and 8 normal control subjects. In each group, a significant linear correlation was found between PaCO2 and VE. The slopes of the regression curves relating PaCO2 to VE were significantly steeper in the healthy control subjects and diabetic patients without AN than in those with AN (P < 0.01). We conclude that the ventilatory response to progressive hypercapnia is reduced in diabetic patients with AN. By analyzing the power spectrum and the amplitude behavior of the diaphragmatic EMG (calculated from the fc and RMS, respectively), we could exclude a disturbance of neural descending pathways and respiratory muscle dysfunction as possible causal mechanisms for the impaired ventilatory response to increasing CO2. By using lung function analysis, causal factors such as alterations in respiratory system mechanics also could be excluded. As diabetes is known to affect the endogenous opioid system, which, in turn, affects the ventilatory response to CO2, naloxone, as a specific opioid antagonist, was administered in all 3 test groups. Naloxone produced a significant increase of ventilatory response to hypercapnia in the healthy control subjects (P < 0.01), but produced no effect in either of the diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Recurrent hypoglycemia and lactate acidosis in non-Hodgkin's lymphoma]. / Rezidivierende Hypoglykämien und Lactatacidose bei Non-Hodgkin-Lymphom.

Two weeks after partial resection of the small intestine for an intra-abdominal stenosing centroblastic non-Hodgkin lymphoma, a 65-year-old man began to experience recurrent attacks of hypoglycaemia (down to 30 mg/dl) together with lactic acidosis (lactate 5.13 mmol/l), tachycardia and sensations of heat. Very high parenteral glucose input (up to 750 g/day) was necessary to maintain normal blood sugar levels. There was close correlation between the level of glucose consumption and the degree of lactic acidosis. After chemotherapy the abnormalities improved, but recurred as the neoplasm proliferated once more. An endocrine mechanism for the hypoglycaemic attacks was excluded by the low serum concentrations of insulin and of "insulin-like growth factors" I and II and by the fact that the levels of glucagon, glucocorticoids, growth hormone and thyroid hormone were within the normal ranges. There were pleural and peritoneal effusions containing large numbers of tumour cells. Investigated in vitro, the fluids showed a decline in glucose and a rise in lactate concentration. Studies with an artificial pancreas also showed that glucose utilization rate in vivo was increased to four times the normal and that it could be raised still further by insulin stimulation. These findings provide evidence of direct consumption of glucose by the tumour cells in the form of abnormally increased anaerobic glycolysis.

Prosthetic support for unilateral facial paralysis.

Removable prostheses were used to determine that esthetics and speech could be improved for patients with permanent unilateral facial paralysis. Esthetics had to be compromised somewhat to obtain the maximum benefit for intelligible speech. This procedure can be beneficial in helping patients who are high surgical risks or for whom surgery, for various reasons, is unacceptable.