Differences in muscle metabolism in patients with type I diabetes - influence of gender and nephropathy studied by (31)P MR spectroscopy.

Type I diabetes mellitus (DM1) is a complex disease with adverse effects on organs and tissues despite compensation by insulin treatment. The goal of our study was to study how kidney diseases change (31)P MR parameters of muscle metabolism in DM1 patients with respect to gender. 51 DM1 patients (19 m/14 f without and 13 m/5 f with nephropathy) and 26 (14 m/12 f) healthy volunteers were examined using (31)P magnetic resonance spectroscopy at 3T tomograph at rest, and during and after a calf muscle exercise. The exercise consisted of a six-minute plantar flexion using a pedal ergometer followed by a six-minute recovery. It is reflected by reduced relative beta-ATP and increased Pi and phosphodiester signals to phosphocreatine (PCr) at rest and prolongation of the PCr recovery time after the exercise. Measurement on healthy volunteers indicated differences between males and females in pH at the rest and after the exercise only. These differences between patients groups were not significant. We have proven that nephropathy affects the metabolism in diabetic patients and our results confirm significant difference between patients with and without nephropathy. Gender differences in pH were observed only between male and female healthy volunteers.

[Angiotensin converting enzyme inhibitors increase insulin sensitivity in offspring of families with hypertension even after active interventions. Results of a clamp study]. / Inhibitory angiotenzin konvertujícího enzymu zvysují citlivost na inzulin i po aktivní intervenci u skupiny potomku z rodin hypertoniku. Výsledky clampové studie.

BACKGROUND: Altered insulin sensitivity is the basis for the syndrome of insulin resistance generally known as metabolic syndrome. Its importance is due to the cumulation of a number of risk factors of IHD. The familial disposition for the syndrome may be the cause of medical complications also in families of hypertensive patients. The objective of the study was to provide evidence of the possible change of insulin sensitivity in a group of middle-aged men from families with disposition for hypertension two years regime therapy and subsequent administration of angiotensin converting enzyme inhibitor (ACEI). METHODS AND RESULTS: Using the method of hyperinsulin euglycaemic clamp a group of 15 offspring of hypertensive subjects (PHT) were examined who at the time did not differ in basic indicators from a control group of 18 men of similar age. The authors found lower values of glucose consumption (Msubmax), metabolic glucose clearance (MCRsubmax), however statistically significant differences were found in the indexes of insulin sensitivity SI (SI: 46.51% +/- 11.77% vs. 54.28% +/- 7.79%, p < 0.02) and ISI (ISI: 6.6% +/- 3.99% vs. 9.88% +/- 5.05%, p < 0.01). After six weeks of ACEI administration (enalapril 10 mg) the insulin sensitivity in PTH increased significantly in the majority of investigated parameters (MCRsubmax to 9.7 +/- 3.04 mg/kg.min-1, p < 0.05), in indexes of insulin sensitivity (SI to 54.83 +/- 12.9, p < 0.001 and ISI to 9.34 +/- 4.78 mg/kg/min-1, p < 0.01). The insulin sensitivity in PHT who were given ACEI exceeded in some indicators the coresponding values in subgroup of controls which was without medication. After ACEI administration the renin secretion increased and the levels of the plasminogen activator inhibitor (PAI-1) did not change. CONCLUSIONS: ACEI administration improved the insulin sensitivity in a group of 15 men from families of hypertensive subjects. It exceeded the effect of diet and change of regime which had already influenced the symptoms of metabolic syndrome in a favourable way.

[Life prognosis and macrovascular complications 10 years after diagnosis of type 2 diabetes]. / Zivotní vyhlídky a makrovaskulární komplikace deset let po zjistení diabetu 2. typu.

BACKGROUND: Diabetes mellitus which develops in middle age is a serious complication, although its impact is often underrated due to relatively few symptoms and independence on insulin. The authors decided therefore to evaluate in 132 men with recently detected type 2 diabetes serious complications, evaluate the prognostic power of indicators apparent at the time of development of diabetes on the general mortality and macrovascular complications which were manifested within 10 years after detection of diabetes. METHODS AND RESULTS: From a group of men, mean age 50.6 +/- 8.5 years, who were examined in 1985-1986 at the Clinic of Diabetology and Experimental Therapy, IKEM, during this period 20 died (15%). The total mortality correlated with systolic blood pressure (154 +/- 26.2 mm Hg vs 140.5 +/- 16.5 mm Hg, p < 0.05), blood sugar level (8.8 +/- 3.0 mmol/l vs 7.4 +/- 2.7 mmol/l, p < 0.05), alpha 2 globulin levels (6.4 +/- 1.2 vs 5.2 +/- 1.1 g/l, p < 0.01, family history of infarction (p < 0.01) and ischaemic changes on the ECG tracing (p < 0.05). In multiple logistic regression the role of systolic pressure, blood sugar level, family history of infarction and also HDL cholesterol in relation to the status after 10 years was confirmed (r = 0.5378). Clinically confirmed macrovascular complications were evaluated after 10 years in 91 of 112 living subjects. Signs of macroangiopathies (43%) were associated with a higher mean age (54.1 +/- 6.9 years vs 48.0 +/- 8.0 years, p < 0.001), elevated triacylglycerol levels (3.7 +/- 2.7 mmol/l vs 2.35 +/- 1.7 mmol/l, p < 0.01), reduced levels of HDL cholesterol (1.04 +/- 0.27 mmol/l vs 1.15 +/- 0.24 mmol/l, p < 0.05) and elevated Apo B levels (1.27 +/- 0.44 g/l vs 1.06 +/- 0.31 g/l vs p < 0.01). Only a group of 13 men which at the time when diabetes was detected had a history of cardiovascular complications the levels of C peptide were significantly elevated 120 min, after stimulation (2.57 +/- 0.74 pmol/ml vs 1.63 +/- 0.96 pmol/ml, p < 0.05). CONCLUSIONS: Components of the metabolic syndrome conditioned by insulin resistance of tissues are among factors which have an impact on the general mortality as well as on clinical symptoms of macroangiopathies.

[Serum insulin levels affect body constitution, blood pressure, serum lipids and cardiac dimensions. Observations in clinically healthy offspring from hypertensive families]. / Sérové koncentrace inzulinu ovlivnují telesnou stavbu, krevní tlak, sérové lipidy i srdecní rozmery. Pozorování u klinicky zdravých potomku hypertenzních rodin.

BACKGROUND: According to some work hypertension is in a pathogenetic relationship with hyperinsulinaemia or is considered to be the consequence of insulin resistance. It is, however, also known that there exists a familial predisposition for hypertension; according to genetic investigations half the family relatives can suffer from hypertension. In conjunction with these views on the pathogenesis of hypertension and its familial character the authors outlined the following objectives of their investigation: to test clinically and metabolically the condition of the offspring of probands with essential hypertension requiring systematic treatment. The authors investigated in particular indicators of body composition, insulin concentration and its relationship to serum levels and some indicators of lean body mass. METHODS AND RESULTS. There were 48 offspring (25 men and 23 women) from families of 30 probands suffering from hypertension. The mean age of the offspring was 38.4 +/- 7.8 years. They were compared with a group of 72 controls, mean age 35.8 +/- 8.2 years (36 men and 36 women) without a family history of hypertension and diabetes (t-test). The basal insulin concentration (IRI O' = 20.5 +/- 12.8 microU/ml, and 14.3 +/- 7.3 microU/ml resp., p < 0.01) and basal C peptide (O' = 0.59 +/- 0.31 pmol/ml and 0.50 +/- 0.20 pmol/ml resp., p < 0.05) were elevated. The offspring of probands with hypertension had a higher body weight (BMI = 25.3 +/- 3.5 kg/m2 and 23.3 +/- 2.5 kg/m2 resp., p < 0.001) a higher ratio of waist hip circumferences (0.94 +/- 0.1 and 0.87 +/- 0.1 resp., p < 0.001) similarly as blood pressure (131.5 mmHg +/- 11.8 mmHg and 116 mmHg +/- 13.3 mmHg resp., p < 0.001) and blood sugar level (5.29 +/- 0.61 mmol/l and 4.93 +/- 0.39 mmol/resp., p < 0.01). The authors also found differences in the serum cholesterol levels (5.9 +/- 1.3 mmol/l and 5.1 +/- 0.6 mmol/l resp., p < 0.01), HDL cholesterol (1.45 +/- 0.50 mmol/l and 1.65 +/- 0.60 mmol/l resp., p < 0.01) and triacylglycerol trends (1.66 +/- 1.54 mmol/l and 1.37 +/- 0.96 mmol/l resp., p < 0.1). On echocardiographic examination the cardiac dimensions were not enlarged, however, significant relations (linear regression) were proved in offspring in particular as regards the dimensions of the left ventricle and insulin (IRI O-left atrium p < 0.05, IRI 30-left atrium, p < 0.01. C peptide O-left atrium, p < 0.05). Between the body mass index, cholesterol, uric acid HDL-cholesterol the waist/hip ratio on the one side, the dimensions of the left atrium, thickness of septum and posterior wall (p < 0.01-0.001), between insulin and C peptide (p < 0.001) on the other side even closer relations were found. CONCLUSIONS: Elevated insulin concentrations may participate in the development of body composition, they influence the lipid transport and blood pressure in clinically healthy offspring of probands suffering from hypertension. The relationship between the insulin concentration and disposition towards enlargement of the left heart needs more detailed investigation.

[Metabolic sequelae of pancreatic transplantation using two different surgical techniques]. / Metabolické dusledky transplantace pankreatu pri pouzití dvou ruzných chirurgických technik.

BACKGROUND: By transplantation of the pancreas in diabetics type 1 long-term-term independence on exogenous insulin can be achieved. The extent of normalization of the carbohydrate metabolism can depend on the applied surgical technique. The objective of the submitted work was to compare indicators of compensation of diabetes one year after combined transplantation of the kidney and pancreas, using the method of transplantation of a segment of the pancreas with obliteration of the pancreatic duct by a polymer and the method of transplantation of the whole pancreas with drainage of the pancreatic duct into the urinary bladder. METHODS AND RESULTS: The authors examined two groups of recipients, 13 subjects each with full function of the pancreatic graft one year after transplantation where a combined transplantation of the kidney and pancreatic segment (group SP) had been performed or of the kidney and whole pancreas (group CP). The authors investigated the blood sugar level, glycated haemoglobin, intravenous glucose tolerance test, free insulin level and C-peptide as well as some indicators of the lipid metabolism and acid base balance. In both groups normal blood sugar levels were achieved, though the mean values in the course of the day were higher in group SP than in group CP (mean +/- SE 5.48 +/- 0.11 as compared with 4.98 +/- 0.09; p < 0.01). Glycated haemoglobin declined in group SP from the pretransplantation value of 9.31 +/- 0.09 to 6.40 +/- 0.10% and in group CP from 9.49 +/- 0.15 to 4.92 +/- 0.08%. In group CP the glycated haemoglobin after transplantation was significantly lower (p < 0.01), similarly as the coefficient of glucose assimilation (1.83 +/- 0.03 as compared with 1.25 +/- 0.15; p < 0.05). Indicators of the acid base balance did not differ. Recipients in group CP were however permanently treated with bicarbonate. CONCLUSIONS: With both transplantation method it is possible to achieve compensation of diabetes close to normal. The carbohydrate tolerance is however better after transplantation of the whole pancreas.

[The metabolic syndrome, its heredity, methods of detection and clinical significance]. / Metabolický syndrom, dedicnost, zpusob detekce a klinický význam.

BACKGROUND: The metabolic syndrome is a common denominator of a number of risk factors which are associated with type 2 diabetes and serious cardiovascular complications. The symptoms develop on the background of insulin resistance and are associated with hyperinsulinism. They are not manifestations of ageing, but are developing probably on a predisposed background already in young age. METHODS AND RESULTS: In the families of 39 probands with symptoms of the metabolic syndrome (MS) there were 58 offspring, mean age. 26.4 +/- 8.7 years. They were compared with 46 controls matched for age, BMI and sex without a family-history of metabolic diseases. The offspring from the families of probands with MS differed in particular by a lower HDL cholesterol level (1.38 mmol/l +/- 0.31 vs. 1.72 mmol/l 1-0.53, p < 0.001), a higher blood sugar level during the glucose tolerance test (p < 0.01) and a higher level of apolipoprotein B (Apo B, p < 0.01). The stimulated insulin concentration, the IRI sums were highly significantly raised (S IRI 240.9 microU/ml +/- 141 microU/ml vs. 177.1 microU/ml +/- 77.9 microU/ml, p < 0.01), similarly as the C peptide concentrations (S C peptide 7.61 pmol/ml +/- 2.84 pmol/ml vs. 5.02 pmol/ml +/- 1.49 pmol/ml, p < 0.001) which correlated mutually. The great majority of offspring came from parents with hypertension and hyperlipoproteinaemia resp., the rest from diabetic families and families with IHD. In offspring of families of hypertonics there was a lower ratio of linoleic acid in serum phospholipids, contrary to complement (= the other members of the group), in offspring of subjects with hyperlipoproteinaemia there were higher fibrinogen and uric acid levels. The offspring of diabetics had higher mean BMI values, in families of patients with myocardial infarction higher C peptide levels were found. CONCLUSIONS: Already at post-adolescent age there are convincing signs which suggest the possible development of metabolic syndrome in predisposed families, as ensues from a comparison with controls: raised IRI, C peptide and some MS component levels. Linoleic acid as well as fibrinogen, BMI and C peptide concentrations which differed in offspring with different types of family-history from the complement are also related directly or indirectly with hyperinsulinaemia.

[Diabetes mellitus in chronic pancreatitis and insulin sensitivity]. / Diabetes mellitus pri chronické pankreatitide a citlivost na inzulin.

Diabetes mellitus as a specific etiological type of disease is a relatively frequent complication of chronic pancreatitis and is found always after total pancreatectomy. It is not clear whether in the frequently profound hypoglycaemias of these patients also increased insulin sensitivity may participate. Data in the literature are not uniform. The objective of the submitted work was to assess the insulin sensitivity in 10 patients with chronic pancreatitis (confirmed by ERCP) and diabetes and to compare them with 10 controls and 10 diabetics type 2 treated by diet matched for age and body mass index. The effect of insulin was assessed by the method of the 3-hour hyperinsulin euglycaemic clamp (insulin level 75 microU/ml, blood sugar level 5 mmol/l) acording to glucose consumption as glucose Mglu, glucose clearance MCRglu and insulin sensitivity index SI. Patients with pancreatic diabetes did not differ from controls and type 2 diabetics resp. as regards fasting insulin, C peptide level and lipid parameters. The groups did not differ as regards the glucagon level. Patients with chronic pancreatitis and diabetes had a lower insulin sensitivity than healthy controls.

[Relation between serum amino acids and insulin sensitivity (results of a clamp study in offspring of hypertensive patients]. / Závislost mezi sérovými aminokyselinami a citlivostí na inzulin (výsledky clampové studie u potomku hypertoniku).

Hypertension which is part of the metabolic syndrome has frequently a family background. The authors investigated therefore indicators of insulin sensitivity by the method of a hyperinsulinaemic euglycaemic clamp in the offspring of hypertensive probands. In conjunction with the increased interest in the role of muscles in influencing insulin sensitivity the authors were also interested in serum amino acid levels. They examined a group of 15 healthy offspring of hypertonic subjects (PHT) and compared them with a group of 18 healthy volunteers without a family-history of hypertension. PHT had as compared with controls a higher systolic pressure (117 +/- 7.2 mm Hg vs. 106.1 +/- 11.7 mm Hg p < 0.01). In the clamp examination in PHT significantly lower indexes of tissue insulin sensitivity were recorded, SI (46.51 +/- 11.8% vs. 54.3 +/- 7.79%, p = 0.02) and ISI (6.6 +/- 3.99 vs. 9.88 +/- 5.05, p < 0.01). In the PHT group were, in addition to the different ratio of some branched chain amino acids and tyrosine, also relations between indicators of insulin sensitivity and arginine. It is thus obvious that signs of reduced insulin sensitivity are present in PHT already in the preclinical stage. Relations between the altered insulin sensitivity and arginine, the precursor of nitrogen oxide, apparent only in PHT could be a stimulus for seeking associations with endothelial damage described in insulin resistant conditions.

[Serum ferritin, LDL oxidation and risk factors for atherogenesis in healthy offspring of hypertensive patients]. / Sérový feritin, oxidabilita LDL a rizikové faktory aterogeneze u zdravých potomku hypertoniku.

Iron is an important factor in the process of oxidation stress and atherogenesis which is as a rule potentiated in subjects with the insulin resistance syndrome. Hypertension is one of the main components of this syndrome. Ferritin due to its relationship with impaired insulin sensitivity becomes a candidate for a new indicator of insulin resistance. The subject of the present study was to assess whether we shall find in young healthy offspring of hypertensive parents changes in the ferritin level, oxidizability of LDL and whether these are related to parameters of glucose tolerance, insulin secretion and sensitivity. Twelve young (27 +/- 3.6 years) non-obese, normotesive offspring of hypertensive parents were compared with a group of 14 controls. Glucose tolerance, insulin secretion and sensitivity were examined by means of a hyperglycaemic clamp and oGTT. As to the ferritin level, the offspring of hypertensive parents did not differ significantly from controls, differences were not fond in the oxidizability of LDL-C. The glucose tolerance was comparable in the two groups. Offspring of hypertensive parents had however a significantly higher insulin and C peptide level when using the clamp and during the glucose tolerance test (p < 0.05), and a reduced insulin sensitivity (p < 0.05). The negative correlation between the index of insulin sensitivity and ferritin suggests that ferritin could be associated with the syndrome of insulin resistance.

[The effect of elevated blood glucose levels and body weight on the metabolic profile in type 2 diabetes after long-term therapy]. / Vliv zvýseného krevního cukru a hmotnosti na metabolický profil dlouhodobe léceného diabetu 2. typu.

Based on an analysis of data obtained in a group of 145 men and women with type 2 diabetes perssiting for 10.1 +/- 6.6 years who were hospitalized on account of unsatisfactory compensation of diabetes, the authors provided evidence that the fasting blood sugar level is associated with a reduced response of C peptide to an alimentary stimulus, while the excessive weight of the patients has a bearing on the elevated concentration of C peptide on fasting and causes their insulin resistance. The body weight has a bearing on the level of risk factors, i.e. HDL cholesterol, uric acid and in women also triacylglycerols. The elevated blood sugar level influences in a mirror image manner the sodium and potassium level. The relations between the blood sugar level and glomerular filtration draw attention to the interference with the water economy even at blood sugar levels which are still tolerated. The trend of rising potassium levels must be foreseen in case of a poor compensation even in case of insulin treatment of diabetes. The risk of elevated potassium should be taken into account also with regard to indications of antihypertensive treatment. The authors also draw attention to the need of acloser compensation of type 2 diabetes. Early adjustment of the energy metabolism in diabetics deserves priority. When insulin treatment is needed, the all-day requirement should be met by 2-3 doses.

Increased fibrinogen levels in the offspring of hypertensive men. Relation with hyperinsulinemia and the metabolic syndrome.

Epidemiological studies have revealed that elevated fibrinogen concentrations are associated with an increased risk of myocardial infarction, stroke, intermittent claudication, and cardiovascular mortality. The manner in which fibrinogen operates in atherogenesis has not yet been elucidated, but genetic control of fibrinogen levels is partially responsible. Fibrinogen frequently acts in concert with hyperlipidemia, diabetes, hypertension, physical inactivity, and age, variables that are influenced by insulin action. Because the offspring of hypertensive men tend to be hyperinsulinemic and insulin resistant from a young age, we hypothesized that their increased fibrinogen levels might reflect decreased insulin action and thus play a role in the metabolic syndrome. We chose 48 adult offspring (mean age, 38.4 years) of 30 fathers who had been treated for hypertension, and the former were matched by age, body mass index, sex, and smoking habits with 37 control subjects. Elevations in fibrinogen concentration (3.63 +/- 0.93 versus 2.87 +/- 0.54 g/L, P < .001) paralleled increases in blood glucose and insulin levels, estimates of insulin resistance, and blood pressure. In the offspring, in contrast to the control group, correlations between fibrinogen and metabolic-syndrome variables (ie, insulin, glucose, and waist and hip circumferences) were found. In stepwise multiple regression analyses, age and smoking habits were entered as variables in both study groups, but postload insulin and high-density lipoprotein cholesterol were entered as variables in the offspring group only. We propose that familial predisposition influences the relationship between insulin concentration and fibrinogen, an effect that may contribute to the clinical importance of the metabolic syndrome.