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Biomedical subjects

G Schernthaner

Publications and source records attributed to G Schernthaner.

At least 55 records · Page 3Linked to original sources
PubMed1998

Differential expression of receptors for advanced glycation end products on monocytes in patients with IDDM.

Accelerated modification of proteins by glucose terminating in the formation of advanced glycation endproducts (AGEs) is one of the main pathogenetic mechanisms of diabetes-associated complications. One pathway by which AGEs may exert their effects is by interaction with specific receptors initially identified on macrophages, monocytes and endothelial cells. As AGE-induced autocrine upregulation of AGE receptors has been observed in vitro, we hypothesized that AGE-binding might be enhanced in diabetic patients to compensate for the elevated levels of circulating AGEs. We therefore examined the expression of AGE-binding sites on peripheral monocytes, serum levels of AGEs and AGE-induced cytokine production in patients with insulin-dependent diabetes mellitus (IDDM) compared to age-matched, healthy control subjects. In patients, AGE-binding capacity was significantly increased and there was only one class of binding sites, as revealed by Scatchard analysis (1.8 x 10(5) vs 1.4 x 10(5) binding sites per cell). Affinity of binding was, however, similar (Ka 1.5 x 10(6) vs 1.4 x 10(6) mol(-1)). Saturation of binding was reached at 2.0-3.0 micromol/l with AGE-bovine serum albumin (BSA) as ligand. In contrast, cytometry using fluorescein isothiocyanate-labelled AGE-proteins showed no saturability and reversibility of AGE-binding up to 80 micromol/l, indicating non-specific binding in this concentration range. Again, this non-specific binding was significantly higher in IDDM patients. In addition, we found much higher levels of circulating AGEs in patients as compared to controls and studied possible functional consequences of increased AGE binding in vitro, monocyte stimulation by AGEs triggering cytokine release to a similar extent in patients and controls, i.e. independently of the AGE-binding capacity. Our finding of an enhanced overall AGE-binding capacity of peripheral monocytes in IDDM could be instrumental in limiting the plasma concentration of AGEs, the non-specific binding coming into play after saturation of specific binding sites by higher plasma AGE-levels. Both binding strategies may act in concert as "damage limitation mechanisms" in the development of AGE-dependent diabetic complications.

Adult↗
PubMed1998

Initial urinary albumin excretion determines the progression of microalbuminuria in patients with type-2 diabetes and normotensive blood pressure values despite improved metabolic control.

Persistent increased urinary albumin excretion rate (UAER) is associated with increased cardiovascular mortality in type-2 diabetes, however, there are no conclusive data about the progression of advanced UAER in these patients. The present study has investigated the effect of metabolic intervention on the progression in UAER in relation to initial UAER levels. A total of 20 patients with type-2 diabetes and secondary failure to sulfonylurea were observed during 1 year (age, 60 +/- 8 years; HbA1c, 10.8 +/- 1.4%; and duration of diabetes, 17 +/- 10 years) and divided into two groups: group 1 (n = 10; UAER: 51 +/- 35 mg/24 h); and group 2 (n = 10; UAER: 191 +/- 175 mg/24 h). Despite a significant improvement of metabolic control by insulin treatment in both groups (HbA1c: group 1: 11 +/- 1.5 vs. 7.9 +/- 1.2%; group 2: 10.6 +/- 0.9 vs. 9.1 +/- 1.3%, P < 0.001), a progression of UAER was observed in group 2 (191 +/- 175 vs. 331 +/- 237 mg/24 h, P < 0.02), but not in group 1 (51 +/- 35 vs. 41 +/- 24 mg/24 h). Still serum creatinine levels remained normal in all patients during the observation period. The 24 h blood pressure (RR) values in the two groups remained normal under antihypertensive therapy throughout the study (group 1: RR syst: 130 vs. 136 mmHg; RR diast: 80 vs. 81 mmHg, mean arterial pressure (MAD): 89 vs. 93 mmHg; group 2: RR syst: 139 vs. 134 mmHg; RR diast: 78 vs. 75 mmHg, MAD: 97 vs. 90 mmHg). The data shows that in type-2 diabetic patients with normotensive blood pressure values the initial urinary albumin excretion levels determine the progression of UAER. When metabolic control is improved incipient UAER remains constant, but advanced UAER shows progression.

Aged↗
PubMed1998

Concentrations of circulating P-selectin are increased in patients with newly diagnosed insulin-dependent diabetes mellitus.

Endothelial cell activations and/or dysregulations of the coagulation system are crucial parameters for the prognosis of disease in patients with IDDM. Recent data suggest that expression of the adhesion molecules E-selectin and P-selectin are markers of endothelial cell activation and/or platelet activation and might modify immunologic responses after shedding from cell membranes. In patients with newly diagnosed IDDM only limited data on circulating selectins are available. This has prompted us to measure levels of soluble (s) forms of P-selectin and E-selectin in 18 patients with newly diagnosed IDDM and two years after the onset of insulin substitution therapy in comparison to 18 age-matched healthy control subjects. HbA1c and blood glucose levels were significantly higher in patients with new onset diabetes, compared to the same patients after two years of insulin therapy (HbA1c: 12 +/- 3% vs. 7.8 +/- 2%; p < 0.01; blood-glucose: 409 +/- 163 mg/dl vs. 131 +/- 23 mg/dl; p < 0.01), but no correlation between these metabolic parameters and soluble forms of E- and P-selectins were noted. Levels of sP-selectin decreased from 210 +/- 120 ng/ml in newly diagnosed IDDM patients to 127 +/- 75 ng/ml after two years of therapy (p < 0.01) and were similar to those of the control subjects (110 +/- 31 ng/ml). Serum concentrations of circulating E-selectin showed no differences in the three groups (newly diagnosed IDDM: 42 +/- 17 ng/ml; two years later: 43 +/- 19 ng/ml; control subjects: 41 +/- 14 ng/ml; n.s.). Increased levels of sP-selectin together with normal levels of sE-selectin at the onset of IDDM suggest enhanced platelet activation during the initial phase of the autoimmune process and return to baseline levels within two years of the disease.

Adult↗
PubMed1998

Postprandial insulin lispro. A new therapeutic option for type 1 diabetic patients.

OBJECTIVE: For intensified insulin therapy of type 1 diabetes, bolus injection of regular human insulin 30-15 min before a meal is currently recommended. This randomized study is aimed to determine whether insulin lispro (LIS), a new insulin analog with a rapid onset of action, can provide comparable blood glucose (BG) control by injection after the meal. RESEARCH DESIGN AND METHODS: Eighteen type 1 diabetic subjects injected regular insulin (REG) at 40, 20, or 0 min before or LIS at 20 or 0 min before or 15 min after the start of a standardized test meal. BG excursions and area under the curve of BG excursions (AUC) at the six visits were compared by analysis of variance. Hypoglycemic events (BG < or = 2.78 mmol/l) were evaluated in relation to the achieved postprandial BG control. RESULTS: Mean AUC values were 2.00, 2.55, and 3.33 mmol.h.l-1 for REG given 40, 20, and 0 min before the test meal, respectively, and -2.19, -2.15, and 1.98 mmol.h.l-1 for LIS given 20 and 0 min before and 15 min after the start of the test meal, respectively. LIS injected 20 min (-20) or immediately (0) before the meal was significantly more effective in controlling postprandial BG excursion (P < 0.001) than any REG treatment. Postprandial injection of LIS (15) did not compromise postprandial BG control and resulted in less hypoglycemia. REG -40 and LIS -20 were associated with early hypoglycemia, but other hypoglycemic events were equally distributed among groups. CONCLUSIONS: The optimal time for bolus insulin injection was 20 min before the meal for REG and immediately before the meal for LIS. LIS injected immediately after a standard meal provided postprandial BG control at least as good as REG injected from 40 to 0 min before the meal. Postprandial injection of LIS is an attractive new therapeutic option.

Adult↗
PubMed1997

[Lispro-insulin analogs in therapy of diabetes].

Since January 1997 the first insulin analogue, lispro has been approved for clinical use in Austria. Insulin lispro has a more rapid onset of action than regular insulin and can therefore be injected immediately before the meal, providing increased therapeutic flexibility for the patients. In many studies a slight decrease in frequency of hypoglycaemic attacks was reported. Insulin lispro did not alter the glycosylated haemoglobin values in the largest multicentre study, although the postprandial glucose concentrations were significantly lower. There was no increased incidence of allergic or other adverse events. No data have been published as yet on the use of insulin lispro in children under 10 years of age and during pregnancy. Potential advantages and disadvantages of insulin lispro therapy, as well as individual factors pertaining to the patient must be taken into consideration on planing treatment with this new insulin analogue. Patients should be well informed about the different action profile of insulin lispro, especially with regard to exercise.

Adult↗
PubMed1997

Slow gastric emptying in type I diabetes: relation to autonomic and peripheral neuropathy, blood glucose, and glycemic control.

OBJECTIVE: To investigate whether autonomic neuropathy or hyperglycemia plays a crucial etiological role in gastric retention of ingesta frequently found in type I diabetic patients. RESEARCH DESIGN AND METHODS: We investigated the gastric emptying of a radiolabeled semisolid 1,168 kJ meal in 38 female and 45 male patients (age 18-75 years; illness duration 3-46 years). None took drugs affecting gastrointestinal motility. Fasted patients underwent tests of cardiovascular autonomic and peripheral nerve function. Blood glucose levels were determined before and after the scintigraphic recording of gastric emptying. RESULTS: The percentage of meal remaining in the stomach at the end of the 50-min recording time was related significantly to the patients' degree of cardiovascular autonomic neuropathy [r (81) = 0.235, P < 0.028] but not to their degree of peripheral neuropathy, preprandial blood glucose level, HbA1c indicative of glycemic control, diabetes duration, and age. The patients' mean residual percentage of meal was significantly greater than that of 48 healthy subjects, that is, 71.1 +/- 15.1 vs. 53.5 +/- 13.1% [means +/- SD; t (129) = 6.48, P < 0.0001]. The healthy individuals' mean residual percentage + 2 SD was exceeded in 22 patients. CONCLUSIONS: Slow gastric emptying in patients with type I diabetes seems related to the degree of autonomic neuropathy but not to peripheral neuropathy, actual blood glucose, and glycemic control.

Adult↗
PubMed1997

The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone.

OBJECTIVE: To compare the therapeutic effects of the alpha-glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone. RESEARCH DESIGN AND METHODS: After a 4-week placebo run-in period, 201 patients in 18 centers in 4 countries were randomized in a double-blind manner to miglitol (50 mg t.i.d., followed by 100 mg t.i.d.), glibenclamide (3.5 mg q.d/b.i.d.), or placebo for 24 weeks. Efficacy criteria were changes from baseline of HbA1c, fasting and postprandial blood glucose and insulin levels, body weight, and serum triglycerides. RESULTS: Efficacy was assessed in 119 patients who completed the full protocol, and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis. Compared with placebo, mean baseline-adjusted HbA1c decreased by 0.75% (P = 0.0021) and 1.01% (P = 0.0001) in the miglitol and glibenclamide treatment groups, respectively. Blood glucose decreased slightly in the fasting state and considerably in the postprandial state in both treatment groups but not in the placebo group. Fasting insulin levels increased slightly (NS) in all treatment groups; however, postprandial insulin levels decreased with miglitol, while increasing markedly with glibenclamide (P = 0.0001 between all treatment groups). Gastrointestinal side effects (flatulence and diarrhea) occurred mostly in the miglitol-treated patients, while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia. CONCLUSIONS: Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.

1-Deoxynojirimycin↗
PubMed1996

Renal and metabolic effects of 1-year treatment with ramipril or atenolol in NIDDM patients with microalbuminuria.

UNLABELLED: The clinical importance of selection of different antihypertensive drugs for the treatment of diabetic patients is still unclear. Thus we performed a randomised, controlled study in 105 hypertensive non-insulin-dependent diabetic (NIDDM) patients with microalbuminuria over 1 year. Patients received either the angiotensin converting enzyme (ACE) inhibitor ramipril (2.5-5.0 mg/day; in addition 24% of patients also received felodipine) or the beta blocking agent atenolol (50-100 mg/day; in addition 24% of patients also received hydrochlorothiazide). Blood pressure, metabolic control, lipid levels and albumin excretion rate were studied during the follow-up. After 1 year an almost identical fall (p < 0.001) in blood pressure was observed with ramipril (170/100 vs 150/ 85 mmHg, median) and atenolol (180/100 vs 150/ 80 mmHg, median). With ramipril a reduction of total cholesterol (6.3 vs 5.9 mmol/l), of LDL cholesterol (3.8 vs 3.6 mmol/l) and HDL cholesterol (1.3 vs 1.2 mmol/l) was found, whereas triglycerides slightly increased (1.8 vs 2.0 mmol/l). With atenolol a similar reduction of total cholesterol (6.3 vs 5.9 mmol/l), LDL cholesterol (3.8 vs 3.7 mmol/l) and HDL cholesterol (1.4 vs 1.2 mmol/l) and an increase of triglycerides (1.4 vs 1.7 mmol/l) was noted. Metabolic control of the patients was maintained with both ramipril and atenolol treatment. With ramipril treatment urinary albumin creatinine ratio (14.4 vs 13.8 mg/mmol) and creatinine clearance (82 vs 84 ml/min) were constant, but with atenolol an increase of albumin creatinine ratio (13.9 vs 19 mg/mmol, p < 0.001) and a slight decrease of creatinine clearance (80 vs 66 ml/min, p < 0.05, not significant after Bonferroni correction) was observed. IN CONCLUSION: 1-year treatment of NIDDM patients with ramipril or atenolol does not influence metabolic control, the changes in serum lipids were similar. Despite almost identical blood pressure reduction in both groups the albumin creatinine ratio was constant under ramipril, but increased under atenolol treatment.

Adrenergic beta-Antagonists↗
PubMed1996

Cardiovascular mortality and morbidity in type-2 diabetes mellitus.

A representative number of prospective studies clearly indicate that cardiovascular morbidity and mortality is significantly increased in type-2 diabetic patients in comparison with non-diabetic control subjects. The cardiovascular death rate is 4.4 fold increased in those diabetic patients presenting none of the classical risk factors (hypertension, hypercholesterinemia or smoking) compared with age-matched control subjects (MRFIT). A decreased survival rate after myocardial infarction, congestive heart failure and an increased occurrence of silent ischemia are responsible for the poor prognosis of type-2 diabetic patients. Recent studies indicate that haemostatic abnormalities and endothelial dysfunction are important risk factors for coronary events in diabetic as well as in nondiabetic patients. In newly diagnosed type-2 diabetic patients a similar prevalence of myocardial infarction and angina compared to previously known type-2 diabetes was found. The long prediabetic period and clustering of risk factors may be very relevant for the high prevalence of cardiovascular disease already at diagnosis of type-2 diabetes. More recent studies performed in Scotland and Verona demonstrated a mortality risk approximately only 50% higher than in nondiabetic subjects. The reduction in the mortality risk could reflect an improvement in diabetes prognosis from the 1960s to the 1980s. Recent observations in type-2 diabetic patients from Finland indicate that glycemic control is an important predictor for coronary heart disease morbidity and mortality. However incidence of coronary heart disease is only low in those patients presenting with a HbAlc value below 6.0%. More information will be available after analysis of the United Kingdom prospective diabetes study. (UKPDS).

Cardiovascular Diseases↗
PubMed1996

Nondipping of nocturnal blood pressure is related to urinary albumin excretion rate in patients with type 2 diabetes mellitus.

Although cardiovascular and cerebrovascular morbidity and mortality in type 2 diabetic patients is closely related to urinary albumin excretion rate (UAER), the causative mechanisms are not yet identified. The aim of our study was to define the circadian variation of blood pressure (BP) in 72 type 2 diabetic patients (mean age 60 years, mean diabetes mellitus duration: 12 years) in comparison with 41 nondiabetic controls with essential hypertension (mean age 58 years) by using ambulatory blood pressure measurement. Thirty diabetic patients had normal UAER (< 30 mg/24 h), 27 had microalbuminuria (30 to 300 mg/24 h), and 15 had persistent proteinuria (> 300 mg/24 h). Systolic blood pressure during both nighttime and daytime was significantly elevated in type 2 diabetic patients with macroalbuminuria compared to controls and patients with normal UAER. During nighttime even type 2 diabetic patients with microalbuminuria had significantly elevated systolic blood pressure compared to controls with essential hypertension. We also observed a correlation of nocturnal blood pressure to UAER (systolic: r = 0.32, P < .007 and diastolic: r = 0.24, P < .04). Nondipping (defined as a reduction of nocturnal BP < 10%) was observed in 80% of the macroalbuminuric, 74% of the microalbuminuric, but only in 43% of the normoalbuminuric type 2 diabetic patients and in 37% of the controls (P < .04). Since a loss of circadian variation of BP is closely related to vascular complications in nondiabetics, our findings may indicate an important relationship between nondipping of BP and the high morbidity and mortality rate in diabetic patients with increased UAER.

Albuminuria↗
PubMed1996

Pulmonary dysfunction in type 1 diabetes in relation to metabolic long-term control and to incipient diabetic nephropathy.

UNLABELLED: The available data on pulmonary function in type 1 diabetes are still conflicting. Recently, restrictive alterations of pulmonary function were demonstrated in type 1 diabetic patients with end-stage renal failure (diabetic nephropathy), whereas patients with kidney failure from other causes had normal pulmonary function test results. In this study, the prevalence and nature of pulmonary dysfunction in type 1 diabetes and the relationship of pulmonary function tests to incipient diabetic nephropathy and metabolic long-term control were analyzed. Pulmonary function tests were performed in long-standing type 1 diabetic patients (n = 39) with normal serum creatinine levels (< 1.3 mg/dl) and the results compared with those of healthy control (n = 44). The patients were divided into those with a normal urinary albumin excretion rate (AER; n = 21, < 30 mg/day) and those with microalbuminuria (n = 18, AER 30-300 mg/day). We found a significant reduction of the following pulmonary function tests (performed by standardized spirometry and wholebody plethysmography) as compared with controls (C) in diabetic patients with microalbuminuria (M) and in diabetic patients with normoalbuminuria (N): total lung capacity (TLC; % predicted: M 89.6, p < 0.004; N 98.5, p = NS; C 101.1), vital capacity (VC; % predicted: M 83.7, p < 0.001; N 90.2, p < 0.03; C 97.3), forced expiratory volume in 1 s (FEV1; % predicted: M 81.2, p < 0.002; N 88.8, p < 0.02; C 93.8), and diffusing capacity of the lung for CO (DLCO; % predicted: M 83.4, p < 0.04; N 92.4, p = NS; C 95.6). We also found a slight increase of the airway resistance (kPa/l/s: M 0.22, p < 0.03; N 0.2, p = NS; C 0.18). The differences in TLC (% predicted) between diabetic patients with normo- and microalbuminuria were significant (p < 0.04). Further a close relation of pulmonary function tests to metabolic long-term control (mean values of repeated HbA1c measurements) was observed: TLC (% predicted: M r= -0.61, p < 0.007, N p = NS), VC (% predicted: M r = -0.57, p < 0.01; N r= -0.59, p < 0.005), and FEV1 (% predicted: M r = -0.50, p < 0.03; N r= -0.62, p < 0.003). IN CONCLUSION: pulmonary dysfunction in long-standing type 1 diabetic patients is more pronounced in patients with increased AER. Typical features of restrictive pulmonary defects, namely a reduction of TLC (% predicted) plus DLCO (% predicted) were observed predominantly in patients with incipient diabetic nephropathy. The clear correlation of pulmonary function tests with HbA1c measurements stresses the importance of optimal metabolic long-term control in type 1 diabetes.

Adult↗
PubMed1996

A case of malignant mastocytosis with circulating mast cell precursors: biologic and phenotypic characterization of the malignant clone.

The phenotypic and biologic properties of malignant cells in a case of aggressive mastocytosis with multi-organ involvement, circulating mast cell precursors and absence of skin infiltrates were analyzed. Circulating mast cell precursors were detected by immunostaining using antibodies against mast cell tryptase as well as by electron microscopy. These progenitors were tryptase+/chymase- (MCT) and accounted for 10 to 20% of nucleated mononuclear blood cells (MNC). A subset of them contained metachromatic granules. As assessed by combined toluidine blue/immunofluorescence staining, the granulated mast cell precursors were found to express CD9 (P24), CD33 (gp67) and CD44 (Pgp-1), but not basophil-related markers (CD11b (C3biR), CDw17 (lactosylceramide), CD123 (il-3R alpha))or monocyte-related antigens (CD14, CD15). Expression of the mast cell growth factor (MGF) receptor, c-kit(CD117), was also demonstrable, whereas the skin mast cell marker C5aR (CD88) could not be detected on mast cell precursors. The ligand of c-kit, recombinant human (rh) stem cell factor (SCF = MGF), induced histamine release from circulating mast cell progenitors, whereas rhC5a, a potent skin mast cell-/basophil-agonist, was ineffective over the dose-range (10(-9) to 10(-7(M)) tested. Analysis of mast cell antigens in malignant mastocytosis or mast cell leukemias may be helpful to establish a diagnosis and to determine the phenotype of the clone.

Adult↗
PubMed1996

[Evaluation of a new method for determining glycated hemoglobin with monoclonal antibodies (DCA 2000)].

HPLC (High Performance Liquid Chromatography) is commonly regarded as the reference method for HbAlc measurements. However, HPLC requires a relatively large technical staff, expensive laboratory equipment and is rather time consuming. The mobile DCA 2000 instrument determines HbAlc in only 9 minutes, using only one microliter of capillary blood. It uses an immunoassay based on the inhibition of latex agglutination and a monoclonal antibody specific for the glycated N-terminal end of the beta-chain of haemoglobin. In order to determine the reliability of this new method for clinical practice we compared HbAlc measurements on DCA 2000 with HPLC values. A correlation analysis in 283 diabetic patients showed a highly significant correlation between the two methods (r = 0.96; p < 0.0001). In 215 samples (75.7%) the value measured by means of DCA 2000 was lower than the reference value (mean deviation: 0.6% HbAlc), in 58 samples (20.8%) it was higher (mean deviation: 0.39%). In 10 samples the values were identical. The maximum deviations were plus 1.6% and minus 1.3% HbAlc. DCA 2000 is easy to handle and gives rapid and reliable information on long-term metabolic control. Hence, it could be very useful for clinical practice and outpatient departments.

Antibodies, Monoclonal↗
PubMed1995

Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus.

PURPOSE: To investigate whether serum levels of lipid peroxides measured as thiobarbituric-acid-reactive substances (TBARS) differ in type I and type II diabetic patients, whether serum levels correlate with late sequelae of diabetes, and whether serum levels of free vitamin E correlate with levels of lipid peroxidation by-products. PATIENTS AND METHODS: The relationship among lipids, glycosylated hemoglobin A1c (HbA1c), lipid peroxides measured as TBARS, and free vitamin E was determined in 158 patients. Fifteen of the 77 patients with type I diabetes and 39 of the 81 patients with type II diabetes had clinically apparent peripheral vascular disease or coronary artery disease, or both. RESULTS: Compared with control subjects, serum levels of TBARS were found to be significantly elevated (P < 0.001) in diabetic patients, and type II diabetic patients had significantly higher levels (P < 0.001) than type I patients. Both type I and type II diabetic patients with good metabolic control (HbA1c < 6.5%) had significantly lower (P < 0.005) TBARS levels than patients with poor metabolic control, but all groups had higher levels than the control group. Type II patients with angiopathy had significantly higher levels of TBARS than patients without angiopathy. Free vitamin E levels in control subjects and diabetic patients did not differ statistically. CONCLUSION: Serum levels of TBARS were significantly increased in all patients suffering from diabetes mellitus, whereby TBARS levels did not depend on the total amount of circulating lipids. It can be suggested that the enhanced lipidperoxidation is contributed to an increased formation of free radicals in diabetes mellitus.

Adult↗
PubMed1995

Progress in the immunointervention of type-1 diabetes mellitus.

Immunointervention studies with immunosuppressive drugs (Cyclosporin A, Azathioprine) in type-1 diabetic patients after clinical diagnosis demonstrated that improvement of beta-cell function is not sufficient and longlasting. Since 80 - 90 % of the beta-cell mass are already destroyed at onset of type-1 diabetes, intervention studies with nicotinamide and insulin (parenteral or oral) were undertaken in the early phase of type-1 diabetes. However, immunomodulation is restricted to familial cases of type-1 diabetes (only 10% of all cases), since prediction of the disease is not possible in the general population. It cannot be excluded that the described immunintervention may only postpone but not hinder the manifestation of type-1 diabetes. Interventions with tolerance induction by BCG or GAD are promising, but did not yet result in prevention of type-1 diabetes in humans. Finally, the most effective strategy would be primary prevention by vaccination or exposure prophylaxis. Should type-1 diabetes prove to be a disease that is provoked through molecular mimicry, i.e. an immunization by an environmental antigen, then strategies to avoid contact with the environmental trigger (f.e. cow's milk protein) or to vaccinate against it (f.e. Coxsackie virus protein P2-c) could be adopted. If all these interventions are not effective in the long term run, research should be concentrated on molecular approaches after improvement in gene transfer technology.

BCG Vaccine↗