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Biomedical subjects

S Witt

Publications and source records attributed to S Witt.

At least 73 records · Page 4Linked to original sources
PubMed1984

Prevalence of islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in children and adolescents with antecedent mumps infection).

There is good evidence that viruses may play a role in some animal models of diabetes. Since mumps virus seems to be the most likely candidate, we studied the possible relationship of islet cell antibodies, islet cell surface antibodies and glucose tolerance in 86 children and adolescents in whom mumps infection had occurred 14 months previously. Impaired glucose tolerance was diagnosed in 3.5% (n = 3) but symptomatic diabetes did not appear. No relationship existed between complications of antecedent mumps infection (pancreatitis, orchitis, meningitis) and glucose tolerance. The prevalence of ICA and ICSA was 78% and 36%, respectively. The simultaneous prevalence of ICA and ICSA was 33%. The pathogenetic role of mumps infection and ICA/ ICSA and their possible relation to slow progressive beta cell destruction remains to be elucidated.

Adolescent↗
PubMed1984

Is there a relationship between genetically determined haptoglobin phenotype and insulin-dependent diabetes mellitus (IDDM)?

The possible relationship between genetically determined haptoglobin phenotype and insulin-dependent diabetes (IDDM), circulating insulin antibodies and the occurrence of microangiopathy was studied in 144 IDDM. There were no differences regarding the distribution of Hp-phenotypes in 144 patients in comparison with a control population (n = 1726). Irrespective of the Hp-phenotype, the degree and severity of diabetic complications (retinopathy and/or nephropathy) significantly increased with the duration of diabetes. There was no relationship between Hp-phenotype and diabetic microangiopathy (retinopathy, nephropathy). No association existed between Hp-phenotype and the percentage of insulin antibody binding. Regardless of the Hp-phenotype, the insulin antibody concentration decreased with increasing duration of diabetes. Insulin binding parameters (maximum binding capacity and equilibrium dissociation constant) were found to vary considerably with the Hp-phenotypes among IDDM. For a given duration of diabetes the equilibrium dissociation constant increased significantly in the range from Hp 1-1, Hp 2-1 to Hp 2-2 phenotype. There was a direct relationship between the logarithm of the equilibrium dissociation constant and the degree of metabolic control, i.e. the lower the dissociation constant the better the metabolic balance. In conclusion, the results do not provide support for a putative relationship between Hp-phenotype and IDDM. However, differences between insulin binding parameters, in dependence on the Hp-phenotype may be of clinical importance.

Adolescent↗
PubMed1984

Monoclonal antibodies to human insulin and their antigen binding behaviour.

Mouse monoclonal antibodies were raised against human insulin by somatic cell hybridization using the mouse myeloma line P3-X63-Ag8. Five cell lines were grown as ascites producing tumors. Insulin binding data were determined from six monoclonal antibodies by Scatchard analysis. Each anti-insulin hybridoma antibody gave a straight-line Scatchard plot confirming the homogeneity of their binding sites and their monoclonality. The equilibrium dissociation constants ranged from 2.20 X 10(-8) to 4.48 X 10(-10) mol/l. We could demonstrate positive as well as negative cooperativity of monoclonal insulin antibodies by performing insulin binding studies with defined mixtures of two different anti-insulin hybridoma antibodies.

Animals↗
PubMed1983

[Mumps - risk for the manifestation of insulin-dependent (type I) diabetes mellitus?].

A series of findings of animal experiments as well as epidemiological and clinical observation speak for the fact that viral infections may play a part as trigger mechanism within the etiopathogenesis of type I diabetes mellitus. Directly or via immune and/or autoimmune processes viruses might start a beta-cell-destructing process. A mumps infection is most frequently brought in connection with a diabetes manifestation. The attempt of a critical valuation of the arguments for a viral etiology of the type I diabetes mellitus is made. Including first preliminary results of the own working team, the authors get the opinion that at present it is not without doubt to prove a causal connection between mumps infection and the development of a type I diabetes mellitus. Prospective investigations including humoral and cellular immune phenomena in relation to the beta-cell-destructing process are to be demanded.

Child, Preschool↗
PubMed1983

Further support for heterogeneity of insulin response and insulin sensitivity in non-obese subjects with glucose intolerance.

The relationship of insulin secretion and insulin sensitivity was studied in 67 age- and body weight-matched non-obese subjects, classified as having a normal glucose tolerance or glucose intolerance (50 g oral glucose load). Insulin response was studied by means of a 2 h glucose infusion. For the determination of insulin sensitivity a 1 h priming dose-constant insulin infusion technique was used. The per cent decrease of plasma glucose level at comparable steady-state insulin levels served as a measure of body sensitivity to exogenous insulin. In patients with glucose intolerance the early (delta IRI area 0-5 min) and late (delta IRI area 30-120 min) insulin responses to iv glucose were significantly reduced in comparison to controls. Controls and subjects with glucose intolerance showed considerable heterogeneity of insulin responses. Patients with glucose intolerance and relative insulin deficiency were not less responsive to insulin than subjects with normal glucose tolerance. There was, however, a wide variation of insulin sensitivity within the two groups. There was a weak significant inverse correlation between insulin response to glucose and insulin sensitivity for the two groups combined and for controls and subjects with glucose intolerance separately. The results demonstrate that the majority of non-obese patients with glucose intolerance and relative insulin deficiency does not exhibit a reduced responsiveness to insulin and therefore hypoinsulinaemia but not insulin resistance is the primary defect for an abnormal glucose tolerance in these group of subjects.

Adult↗
PubMed1982

[Effect of a combined diet-training program on the insulin sensitivity of obese persons with normal or disordered glucose tolerance].

The majority of the obese persons is characterized by a disturbed glucose tolerance and an increased insulin secretion. The cause of this apparent contradiction lies in the existence of an insulin resistance. In 23 obese persons (relative weight greater than 120% according to Möhr and Johnson) with normal or disturbed glucose tolerance the effect of a diet restriction lasting 4 weeks (700 kcal/die) or of a combined diet training programme on the body weight, serum lipids, state of conditioning (PWC170) and insulin sensitivity in vivo was investigated. The insulin sensitivity was characterized by means of 1 h insulin infusion test. At comparable peripheral steady state insulin levels the relative decrease of the plasma glucose and free fatty acid concentration is a measure of the insulin sensitivity in vivo. In 9 obese persons with disturbed glucose tolerance observations of the course over 1 year are existing. The finding demonstrate that only a combined diet training programme leads to a significant improvement of the insulin sensitivity and prevails a unique dietary treatment. The measure of the improved insulin effectivity directly correlates with the effect of conditioning. The reduction of the body weight obtained is about double as large in a combined diet conditioning treatment as after a unique restriction of the diet (18% or 10% of the relative weight). Triglyceride and cholesterol levels significantly decrease, the HDL-cholesterol increases in tendency. On the other hand, the results are unsatisfactory after one year. The therapy regime is a promising strategy for the reduction of the insulin resistance in adiposity as a preventive medical measure, provided a good cooperation and motivation on the side of the patient is present.

Blood Glucose↗
PubMed1982

Discrepant effect of the prostaglandin synthesis inhibitor acetylsalicylic acid on insulin and C-peptide response to glucose in man.

The prostaglandin synthesis inhibitor acetylsalicylic acid (ASA) increases acute insulin response to glucose and improves glucose tolerance in man. In an effort to provide further information on the mechanism whereby ASA improves glucose tolerance, we studied the effect of ASA on C-peptide, insulin, pancreatic glucagon (IRG), growth hormone (HGH), nonesterified fatty acids (NEFA) and glycerol responses to glucose in 11 non-obese subjects with impaired glucose tolerance. The glucose tolerance was evaluated by means of a 2 h-glucose infusion test. A daily treatment with 3.0 g ASA over 3 days caused a significant increase of acute (delta IRI area 0-5 min) and late (delta IRI area 30-120 min) insulin response and an improvement of glucose tolerance. By contrast, C-peptide response was in the same range prior to and after ASA treatment. Thus, the C-peptide/insulin ratio was decreased by about 50% due to ASA treatment. IRG, HGH, NEFA and glycerol responses to glucose were not altered by ASA treatment. In summary, the discrepant effect of ASA on C-peptide and insulin responses suggest that changes of insulin metabolism may be involved in the mechanism of ASA induced increase in peripheral insulin levels. The improvement of glucose tolerance after ASA application seems to be related to the biologic effect of higher circulating insulin levels but not to alteration of insulin antagonists, such as IRG, HGH and NEFA.

Adult↗
PubMed1982

Evaluation of insulin resistance in non-obese subjects with impaired glucose tolerance.

Insulin resistance was estimated in nine subjects with impaired glucose tolerance (IGT) and eleven healthy, age and body-weight matched controls. Glucose tolerance and insulin response were evaluated by means of a 2h-glucose infusion test. Insulin resistance was determined by measuring the steady state plasma glucose response (SSPG) to a continuous infusion of glucose (6 mg . kg-1 . min-1 or 12 mg . kg-1 . min-1), insulin, epinephrine and propranolol for 150 minutes as described previously by other authors. The endogenous insulin secretion (C-peptide) was inhibited by epinephrine and propranolol in controls and subjects with IGT irrespective of a low (6 mg . kg-1 . min-1) or high (12 mg . kg-1 . min-1) glucose infusion. Steady-state plasma levels of exogenous insulin were virtually identical in all groups studied. There were no significant differences in the pancreatic glucagon, growth hormone, FFA and glycerol response during the SSPG period between controls and subjects with IGT. In comparison to controls the mean SSPG was significantly higher in subjects with IGT (during low and high glucose infusion) suggesting the existence of insulin resistance in these subjects. A higher glucose dose as described earlier by other investigators does not provide a better discrimination of controls and subjects with IGT concerning their degree of insulin resistance. Finally, there was a direct correlation between the SSPG and glucose tolerance in the total group. In conclusion, our results have confirmed the validity of an infusion technique of glucose, insulin, epinephrine and propranolol for evaluation of insulin sensitivity in vivo. In addition, our findings have added further support for insulin resistance in subjects with IGT which is directly proportional to the degree of glucose intolerance.

Blood Glucose↗
PubMed1981

[Effect of glibenclamide therapy on carbohydrate and lipid metabolism and insulin secretion in patients with glucose tolerance disorders : a 5-year study].

In normal weight persons with impaired glucose tolerance (IGT; normal fasting glycaemia and pathological glucose tolerance) and still normal or already decreased insulin secretion the influence of glibenclamide (maninil) on the carbohydrate and lipid metabolism as well as the insulin secretion was studied after one year (n = 18), after 2 years (n =13), after 3 years (n = 10) and after 5 years (n = 6). Glucose tolerance and insulin secretion were characterized by means of a 2 hours' glucose infusion test (0.33 g/kg as bolus and 12 mg/kg/min over 120 min). In no case the diabetes became manifest during the 5-year duration of the observation. An improvement of the glucose tolerance could be observed up to 3 years, whereas after a 5-year glibenclamide therapy no certain influence on the glucose tolerance and insulin secretion could be proved. In general the improvement of the glucose tolerance was not associated with an increased secretion of insulin, so that an extrapancreatic effect of glibenclamide (improvement of the peripheral insulin sensitivity?) seems to be possible. A complete normalization of the glucose tolerance could be observed only in some individual cases. The body-weight remained constant in all groups, whereas the concentration of triglyceride and cholesterol decreased in their tendency. From clinical and practical point of view the findings would support the opinion that normal weight persons with IGT, particularly in already decreased insulin secretion, have an indication for a glibenclamide therapy.

Blood Glucose↗
PubMed1981

[The HLA system and diabetes mellitus].

Diabetes is a heterogeneous disease, and its pathogenesis and etiology are still largely unknown. Recent studies have brought new knowledge showing that HLA antigens and diabetes mellitus are related. It has been found that the relative risk of juvenile onset diabetes requiring insulin treatment is greater for persons who are HLA-A1, A2, B8, BW15, BW40, CW3, DW3, DW4, DRW3 and DRW4 positive. The relative risk of the disease is additive in persons who have two of the above mentioned HLA-B alleles. Some HLA antigens (HLA-B7, DW2, DRW2, A11) are associated with a significantly lower risk of the disease and probably have a "protective" character. Maturity onset diabetes (MOD) and maturity onset diabetes not requiring insulin treatment (MODY) are not related to the HLA system. This means that MOD is completely distinct from JOD with different symptoms, course and etiopathogenesis.

Diabetes Mellitus↗
PubMed1981

Evaluation of insulin resistance during inhibition of endogenous insulin and glucagon secretion by somatostatin in non-obese subjects with impaired glucose tolerance.

Insulin resistance was studied in seven non-obese male subjects with impaired glucose tolerance and four healthy, age and body-weight matched male control subjects by means of a continuous intravenous infusion of somatostatin, glucose and insulin over 150 min. Glucose tolerance was evaluated by means of a 2-h glucose infusion test. Endogenous insulin (C-peptide), growth hormone, and glucagon secretion were suppressed by somatostatin in both groups. Steady-state plasma insulin and glucose levels were achieved between 90-135 min. Since similar steady-state levels of exogenous insulin were achieved, the resulting steady-state plasma glucose level provided a direct estimate of the ability of insulin to dispose of the infused glucose. The glucose levels were higher in subjects with impaired glucose tolerance with values of 14.6 +/- 1.8 mmol/l compared with 5.1 +/- 1.2 mmol/l in control subjects (p less than 0.01), thus indicating insulin resistance. There was a direct correlation between the steady-state plasma glucose level and glucose tolerance suggesting that the degree of glucose intolerance is proportional to the degree of insulin resistance. These results revealed that decreased insulin sensitivity is found in non-obese subjects with impaired glucose tolerance.

Adult↗
PubMed1981

Pancreatic glucagon response to glucose in obesity with normal and impaired carbohydrate tolerance.

Pancreatic glucagon (IRG) and insulin (IRI) secretion patterns were studied in obese subjects with normal (n = 7), borderline (n = 5) and pathological carbohydrate tolerance (n = 11), as well as in 19 non-obese healthy controls without a family history of diabetes, by means of a 2-h glucose infusion (12 mg/kg/min), primed by an initial injection of 0.33 g/kg glucose. With regard to the insulin secretion all obese groups were characterized by a significant hyperinsulinaemia during the late secretion phase, whereas the early insulin response ( delta IRI-area 0-5 min) was significantly reduced in obesity with pathological carbohydrate tolerance. There was no significant differences in fasting IRG levels among controls (29.7 +/- 6.1 pmol/l) and pathological glucose tolerance (31.2 +/- 4.6 pmol/l). In addition, absolute IRG levels and the IRG concentration pattern during glucose infusion were comparable in all groups confirming no alpha-cell resistance to glucose suppression in obesity, irrespective of normal or impaired carbohydrate tolerance. The molar IRI-IRG ratio was significantly increased during glucose infusion in all obese groups reflecting a relative anabolic state. There were no correlations between IRG secretion and relative body weight, glucose tolerance or insulin response to glucose.

Adult↗
PubMed1981

Changes of early insulin responses to glucose in obese subjects with normal and impaired carbohydrate tolerance.

We have studied changes in the sensitivity of the early insulin response to glucose by means of an intravenous pulse-stimulation of 1.0 g, 2.5 g and 5.0 glucose at intervals of 30 min in 24 non-obese healthy controls without a family history of diabetes and in obese subjects with normal (n = 7) and pathological carbohydrate tolerance (n = 23). All subjects were characterized regarding carbohydrate tolerance (CHT) by using a 2 h-glucose infusion test (GIT; 12 mg/kg/min), primed by an initial injection of 0.33 g/kg glucose. Compared with controls the early insulin response (delta IRI-area 0-5 min) during GIT was slightly increased in obesity with normal CHT and it was significantly reduced in obesity with pathological CHT. With regard to the late insulin response phase (delta IRI-area 30-120 min) both obese groups were characterized by a significant hyperinsulinemia. During staircase glucose stimulation a dose-dependent significant increase of the maximal IRI-response was observed in controls whereas this strong relationship was lacking in the two obese groups. The dose-response curve in obesity with normal CHT was displaced toward the left of the control curve whereas a right shift was found in obesity with pathological CHT. There was a significant correlation between early insulin response during GIT and maximal insulin response revealed by staircase glucose stimulation in obese subjects with pathological CHT. No close relationship of this type could be detected in the other groups so far studied. Our findings suggest an increased sensitivity of the beta-cells to glucose in the hyperinsulinemia stages of obesity with normal CHT. In contrast to this, a reduced sensitivity of the early insulin response to glucose is suggested in obesity with pathological CHT. A staircase glucose stimulation seems to be a useful tool in studying the early insulin response to glucose.

Blood Glucose↗
PubMed1981

Investigation of insulin sensitivity in early diabetes III. The effect of a combined physical training and diet programme on body weight, serum lipids and insulin sensitivity in obese asymptomatic diabetics.

The effect of a physical training and low caloric diet (700 calories/day) for 4 weeks on insulin sensitivity in vivo, body weight and serum lipids was investigated in 10 obese asymptomatic diabetics (normal fasting plasma glucose and pathological glucose tolerance). Glucose tolerance and insulin secretion pattern were characterized by means of a 2h-glucose infusion test (12 mg/kg/min) primed by an initial injection of 0.33 g/kg glucose. Insulin responsiveness in vivo was estimated by means of a 1h-insulin infusion test (two 30-min. periods of 8 and 16 mU/kg insulin MC-Actrapid, primed by initial injection of 1 and 2 mU/kg, respectively). Under comparable steady-state insulin levels the decrease in plasma glucose and free fatty acids (FFA) was considered as estimate of insulin sensitivity in vivo. Physical working capacity (PWC170) was determined by means of a bicycle ergometer test in stepwise working loads. The training programme consisted of daily 15 min. bicycle ergometer training periods (75% of the maximal working capacity) in the morning and a 1 h mild physical training on a bicycle in the afternoon. After the combined training and diet programme the mean decrease in absolute and relative body weight amounted to 11.9 +/- 1.07 kg and 16.7 +/- 1.2%, respectively. There was a significant decrease of plasma triglycerides whereas the decrease in cholesterol was modest. Physical fitness increased by delta PWC170 of 31.1 +/- 11.6 W. In addition, the combined training and diet programme for 4 weeks resulted in a significant improvement of insulin sensitivity in vivo as indicated by an augmented insulin-induced decrease in plasma glucose and FFA (17.60 +/- 3.91%, vs 36.40 +/- 5.54%; p less than 0.05 and 35.90 +/- 6.95% vs 56.50 +/- 3.63%; p less than 0.05; respectively). Our findings provide direct evidence that physical training and low caloric diet enhance insulin sensitivity in vivo. From the practical point of view our results suggest the potential benefits of physical training in the treatment of obese asymptomatic diabetics.

Adult↗
PubMed1980

[Spontaneous changes in carbohydrate tolerance and insulin secretion in persons with indications of disturbed carbohydrate tolerance. Preliminary results and follow-up observations for 7 years].

115 patients with normal weight and 15 adipose persons with suspicion of a disturbance of the carbohydrate metabolism were characterized by means of a glucose infusion test lasting two hours concerning the carbohydrate tolerance and insulin secretion. Longitudinal analyses of the spontaneous behaviour of the carbohydrate tolerance and insulin secretion depending on the degree of the carbohydrate tolerance up to duration of the observation of 7 years. A deterioration of the carbohydrate tolerance was to be proved in 21% of 87 persons with normal carbohydrate tolerance within two years. With normal carbohydrate tolerance within two years. With an increase of the duration of the observation up to 7 years the frequency of disturbances of the carbohydrate tolerance increases to 30%. This development cannot be coordinated to a certain type of insulin secretion. In the individual case a deterioration of the carbohydrate tolerance may be associated with an increase or reduction of the glucose stimulated insuline secretion. An improvement of the carbohydrate tolerance was observed in 15 (54%) of 28 patients with disturbed carbohydrate tolerance within 2 years. In a group with pathological carbohydrate tolerance this development was associated with a significant reduction of the basic and glucose stimulated insulin secretion. In all patients with improved carbohydrate tolerance on the side of the insulin secretion primarily the type of "normal response" was present. The lacking relation between changes of the B-cell function and the carbohydrate tolerance emphasizes the importance of other factors, such as a peripheral insulin resistance, for the development of disturbances in the carbohydrate metabolism.

Carbohydrate Metabolism↗