[Strategies for early detection of the risk of type II (non-insulin-dependent) diabetes in 1st degree relatives of patients with this disease]. / Model postepowania umozliwiajacego wczesne wykrywanie zagrozenia cukrzyca typu 2 (insulinoniezalezna) u krewnych I stopnia osób ze znana postacia tej choroby.

UNLABELLED: The present study included two groups of subjects: I. the adult offspring of parents with conjugal type 2 diabetes (n = 77; age range 18-59 yrs and mean age 38 +/- 0.8 yrs; BMI range 18.9-40.3 kg/m2 and mean value 26.6 +/- 0.6 kg/m2); and II. the adult offspring having one parent with type 2 diabetes: either father (n = 83-53%) or mother (n = 74-47%). The age range of the latter group was 21-64 yrs, mean age 41 +/- 0.8 yrs; BMI range was 17.6-46.4 kg/m2, and mean value 26.8 +/- 0.4 kg/m2. The normal glucose tolerance of the "healthy" parent was verified with the OGGT evaluated by the WHO and ADA criteria. In all offspring the same test (75 g) was performed, and glucose in venous blood and insulin (IRI) in serum were determined on fasting and at 30, 60 and 120 min of the test. In fasting state the levels of serum lipids (triglycerides, total and LDL and HDL cholesterol and apolipoprotein AI and B) were also measured. In the group I unknown diabetes mellitus was discovered in 4 cases (4%): in 3 according to the WHO/ADA criteria and in one case evaluated by the ADA criteria), in 19 subjects (25%) IGT was found in 16 isolated and in 3 associated with isolated fasting glycaemia (IFG), and only in one case (1%) the isolated IFG was ascertained. In the group II diabetes was discovered according to the ADA criteria in 4 persons (2.5%), IGT in 29 subjects (18.5%), of whom 8 had also IFG. In this subgroup 16 subjects had diabetic father and 13 diabetic mother. The isolated IFG had 7 offspring (4.4%), of whom 2 had diabetic father and 5 diabetic mother. Apart from glycaemia, other parameters didn't disclose difference between the offspring of diabetic father and diabetic mother. However, considering these parameters together for the whole group II, it was found that the offspring with IGT, isolated and associated with IFG, differed from the remaining ones with significantly higher BMI, higher systolic blood pressure, higher 2-h serum IRI, and higher levels of serum triglycerides, total cholesterol and ApoB. CONCLUSION: Measurement of isolated fasting glycaemia and its interpretation by the ADA criteria is inadequate in studies aiming at early detection of glucose intolerance in subjects with familial increased risk of type 2 diabetes and should include also the determination of the 2-h glycemia of the OGTT evaluated according to the WHO criteria. On the other hand, the determination of fasting glycaemia and its evaluation by the ADA criteria is a valuable in diabetes screening, as its elevated level may identify other metabolic disorders associated with diabetes, and unfavorable risk of cardiovascular complications of this disease.

[Glucose tolerance, function of pancreatic B-cells and blood lipids in "healthy" offspring of parents with conjugal type 2 diabetes]. / Tolerancja glukozy, czynnosc komórek B wysp trzustki i lipidy krwi u "zdrowego" potomstwa malzenstw z cukrzyca typu 2 (diabetes coniugum).

In 56 adult normoglycemic nondiabetic (WHO criteria) subjects, whose both parents had type 2 diabetes, and in 68 control probants, matched for age, sex and body mass without family history of diabetes, the OGTT (75 g) was carried out, including measurement of serum insulin (IRI) and C-peptide (CP). In fasting state also the blood lipid profile was determined: serum triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein AI (apoAI) and apolipoprotein B (apoB). In comparison with the control group, the offspring had significantly lower mean glycaemia on fasting, and non significantly elevated from the 60 min of the test, the significantly higher values of serum IRI and CP in fasting state and at the end of the test (120-180 min), and significantly lower serum CP:IRI molar ratio, expressing the reduced hepatic clearance of insulin. The offspring had significantly higher mean values of serum LDL-cholesterol, and significantly lower of serum HDL-cholesterol and apoAI, not disclosing significant differences in the serum levels of triglycerides, total cholesterol and apoB with the control group. Only serum HDL-cholesterol was significantly (negatively) correlated wit serum IRI and CP-values. The covariance analysis, eliminating the influence of age, body mass and the secretory activity of pancreatic B-cells, revealed the significant correlation of the presence of parental diabetes with serum levels of LDL-cholesterol (increase), and HDL-cholesterol and apoAI (decrease) in the offspring. These results prove indirectly, that in subjects genetically predisposed to type 2 diabetes, before the manifestation of glucose intolerance are present other effects of insulin resistance, expressed in increased activity of pancreatic B-cells, increased transfer of insulin to extrahepatic tissues, and in changes of concentration/composition of some lipoproteins dues to reduced influence of insulin on the enzymes which control their metabolism.

[Evaluation of efficacy, safety and tolerance of glimepiride (Amaryl) in patients with type 2 diabetes]. / Ocena skutecznosci, bezpieczenstwa i tolerancji glimepirydu (Amaryl) u pacjentów z cukrzyca typu 2.

UNLABELLED: Glimepiride is a new long-acting the third generation sulfonylurea given once daily. The aim of this study was to evaluate the efficacy, safety and tolerability of glimepiride given as monotherapy in type 2 diabetic patients. A total of 142 patients (65 women and 77 men; mean +/- SD: age 57 +/- 8.5 years, duration of diabetes 64.4 +/- 57.7 months, BMI 28.7 +/- 3.6 kg/m2) were treated during 12 weeks with glimepiride (Amaryl). Glimepiride was forced titrated 0.5-7.0 mg once daily based on efficacy. Statistical analysis our results showed significant (p < 0.001) decrease of average fasting blood glucose, twenty-four hour plasma glucose values and HbA1c significantly lower. Systolic and diastolic blood pressure was also significantly (p < 0.001; p < 0.03) lower. There was a trend to lower serum cholesterol and triglyceride levels. The other laboratory values did not change during this study. No differences were registered in body weight. Safety was assessed by evaluating vital signs, laboratory values and the occurrence of adverse events. The frequency of hypoglycaemic events was very rare (0.7%). The percentage of patients with adverse drug reactions was 6.3%. The tolerance of glimepiride was good. CONCLUSION: This study demonstrates that glimepiride is effective, safe and well tolerated in improving glycaemic control in patients with type 2 diabetes.

[Clinical evaluation of glimepiride in treatment of type 2 diabetes. Results of a multicenter study]. / Kliniczna ocena glimepiridu w leczeniu cukrzycy typu 2. Wyniki badania wieloosrodkowego.

In a multicenter study 142 patients (from 8 centers) with type 2 diabetes (77 men and 65 women, mean age 57 +/- 8.5 (SD) yrs, mean duration of diabetes 64.4 +/- 57.7 months, mean BMI 28.7 +/- 3.6 kg/m2) received over 3 months as the only antidiabetic drug glymepiride (Amaryl) once daily before breakfast in the dose of 0.5-7.0 mg, but mostly 1-3 mg. The treatment was interrupted in one patient due to metabolic deterioration which needed insulin therapy, in an other one because of allergic eruption, and in two because of insufficient compliance. In all other patients the satisfactory decrease of glyceaemia in fasting state and over the day was obtained: the median value of the mean daily glycemia decreased from 8.8 mmol/l (158 mg/dl) to 7.2 mmol/l (129 mg/dl), p < 0.001, of the mean Mw index from 12 to 8.2, p < 0.001, also the median value of HbA1c diminished from 8.0 to 7.35%, p < 0.001. These effects were particularly evident in a subgroup of 28 patients with diabetes duration below 1.5 yrs: at the end of the study no one blood glucose value in the daily profile did exceed 7.7 mmol/l (140 mg/dl). No significant change of BMI, serum triglycerides and serum total cholesterol was observed, instead a significant decrease of mean systolic and diastolic blood pressure took place (from 143 +/- 20 to 136 +/- 17 mm Hg, p < 0.001, and from 85 +/- 10 to 83 +/- 9 mm Hg, p < 0.001, respectively). The tolerance of the drug was good. The verified hypoglycaemia developed in one patient (0.7%). No changes of the laboratory safety parameters were observed.

[Short-term intensive insulin therapy as a method of overcoming secondary failure of sulfonylureas in patients with type 2 diabetes (non-insulin-dependent)]. / Krótkotrwale intensywne leczenie insulina jako metoda przezwyciezania póznej nieskutecznosci pochodnych sulfonylomocznika u chorych z cukrzyca typu 2 (insulinoniezalezna).

UNLABELLED: The study group comprised 56 patients (25 males and 31 females) with type 2 diabetes in whom the secondary failure to sulphonylurea derivates (SU) had developed. All patients were submitted for 14 days to therapy with 5 injections of insulin per day in total dose of insulin permitting to decrease the mean daily glycaemia below 8.8 mmol/l (160 mg/dl). After the termination of the intensive insulin therapy (IIT) the patients with insulin requirement below 44 U daily were alternatively qualified to treatment with SU (glybenclamide) alone or with this SU plus biguanide derivate (BG: phenformin), and those who needed more than 44 U daily continued conventional therapy with insulin alone or with insulin plus SU (glybenclamide). There was a marked reduction of fasting and postprandial blood glucose during the IIT and over the subsequent 15 months of the follow-up. The mean glycaemia which initially was in fasting state 12.5 +/- 2.4 mmol/l (225 +/- 43 mg/dl) and 2 hours after breakfast 18.1 +/- 2.8 mmol/l (325 +/- 50 mg/dl) decreased significantly and was in four groups between 8.0 +/- 0.3 mmol/l (144 +/- 5 mg/dl) and 10.8 +/- 0.5 mmol/l (194 +/- 9 mg/dl) in fasting state and between 10.5 +/- 0.3 (189 +/- 5 mg/dl) and 11.2 +/- 0.4 mmol/l (201 +/- 7 mg/dl) after breakfast. The least hypoglycaemic effect was found in patients who after IIT were treated exclusively with insulin (mean daily dose 53 +/- 2 IU) while the decrease of glycaemia was most evident in patients treated with SU given as a single drug or in combination with BG or with insulin (mean daily dose 19 +/- 1 IU). In all studied patients basal and stimulated (1 mg glucagon i.v.) C-peptide secretion markedly decreased during IIT, and greatly increased after its termination, and this increase persisted over following 15 months of observation, correlating with the initial values. CONCLUSIONS: The short-term IIT in patients with NIDDM and secondary failure to SU is effective in reducing hyperglycaemia, and in most of them makes possible to continue the oral antidiabetic treatment with SU. The secretion of endogenous insulin seems to have only limited influence on the metabolic control of the patients treated with four different pharmacological regiments after IIT.

[Behavior of insulin, C-peptide and proinsulin levels in serum in the course of acute pancreatitis]. / Zachowanie sie stezenia insuliny, peptydu C i proinsuliny w surowicy w przebiegu ostrego zapalenia trzustki.

14 patients with acute pancreatitis during 16 episodes of the disease were studied. The concentration was measured of blood glucose, serum insulin (IRI), serum C-peptide (CP) using two methods: with Byk-Mallinckrodt kits and with more specific M-1221 antibodies Novo, and of serum proinsulin (Pro) in fasting state on days 1, 2, 3, 5 and 10 after the acute onset. Apart from some sporadic rises in the initial period of the disease, the blood glucose level did not change significantly, and had rather a decreasing trend. The mean serum IRI concentration was 0.17 +/- 0.17 (SD) nmol/l, and it decreased on the 5th day to 0.06 nmol/l 0.04 nmol/l, rising again to 0.11 +/- 0.15 nmol/l on the 10th day. The serum Pro concentration was on the same days: 11.1 +/- 12.6, 4.2 +/- 2.4 and 7.5 +/- 10.8 pmol/l, while the serum CP concentration determined with M-1221 antibodies was 0.48 +/- 0.50, 0.34 +/- 0.19 and 0.52 +/- 0.25 nmol/l respectively. However, when for serum CP determinations the Byk-Mallinckrodt kits were used, the concentration of this peptide was on the 1st day 1.90 +/- 1.12 nmol/l, and it decreased over the following days to 1.08 +/- 0.98 on the 5th day, but remained on the same level on the 10th day (1.11 +/- 0.46 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

[Personal experience with combined treatment of gliclazide and insulin in patients with non-insulin-dependent diabetes (type 2) and late secondary failure of sulphonylureas]. / Wlasne doswiadczenie w skojarzonym leczeniu gliklazydem i insulina chorych z cukrzyca nieinsulinozalezna (typu 2) i pózna nieskutecznoscia pochodnych sulfonylomocznika.

The study was carried out on 20 patients, aged 20-60 years, with non-insulin-dependent (type 2) diabetes of 3-17 years duration and with secondary failure of sulphonylurea derivatives. In the initial run-in-period (8 weeks) the patients were treated only with insulin in a dose decreasing glycaemia in fasting state to 160 mg% (8.9 mmol/l), then during 16 weeks they received insulin and gliclazide 160-320 mg per day, and finally during the final period (8 weeks) they were transferred again to exclusive insulin therapy. The association of gliclazide with insulin resulted in better metabolic control expressed by significant decrease of basal and postprandial glycaemia and small (non-significant) decrease of serum triglycerides level--with simultaneous reduction of daily insulin requirement by 34% on the average. In this period an increase of basal and stimulated (test meal) C-peptide secretion was observed. The improvement of the metabolic state and the increased C-peptide secretion persisted also after gliclazide withdrawal (during the second period of exclusive insulin therapy), although the determined parameters were less favourable than when combined treatment was applied. The mechanism of metabolic improvement of patients with type 2 diabetes and secondary failure of sulphonylurea derivatives, which follows the addition of gliclazide to insulin, is not fully clarified. Probably it is the consequence of both, the increased secretion of endogenous insulin and the enhanced activity of this hormone in insulin-sensitive tissues.

[Functional capacity of pancreatic B cells in patients with diabetes mellitus type 2 with late true ineffectiveness of sulfonylurea derivatives]. / Sprawnosc czynnosciowa komórek B wysp trzustkowych u chorych na cukrzyce typu 2 z pózna rzeczywista nieskutecznoscia pochodynych sulfonylomocznika.

Fasting concentration of the C peptide in serum was estimated in 150 patients with type 2 diabetes treated with insulin because of the late, true ineffectiveness of the sulphonylurea derivatives. In 36 patients selected out of the total group at random the secretion of that peptide was measured after i.v. injection of 1 mg of glucagon. Only 9 patients showed trace amounts of that peptide at morning fast (Group A--0.17 +/- 0.08 nmol/l), in 69 the secretion was normal (Sub-Group B1--0.80 +/- 0.25 nmol/l), in 48 moderately elevated (Sub-Group B2--1.67 +/- 0.10 nmol/l) and in 24 markedly elevated (Sub-Group B3--4.54 +/- 2.57 nmol/l). The increments of the peptide C concentration after glucagon stimulation were parallel to its fasting concentration, which indicated a proper reactivity of the pancreatic beta-cells in patients with normal or increased basal secretion. The patients with only trace secretion of the peptide C differed from the other by their small, normal body mass and by a longer duration of insulin treatment. Very similar insulin needs must be stressed in the patients of the Groups A and B as well as within the Sub-Groups B. In patients with hyperactivity of the beta-cells (Sub-Group B2 and B3) no differences were found, as compared with the other patients, in the prevalence of chronic diabetes complications of the micro- or macroangiopathy type, also prevalence of hypertension was equal. The results presented show that in the most patients with type 2 diabetes, with the late, true ineffectiveness of the sulphonylurea derivatives the secretory function of the pancreatic islets beta-cells remains normal or is even increased.

Serum levels of true insulin, C-peptide and proinsulin in peripheral blood of patients with cirrhosis.

The levels of proinsulin, immunoreactive insulin, true insulin (calculated from the difference, namely immunoreactive insulin-proinsulin) and C-peptide were determined in the fasting state and during a 3-h oral glucose tolerance test after administration of 100 g of glucose in 12 patients with cirrhosis with normal oral glucose tolerance test (50 g) and in 12 healthy subjects serving as controls. In the patients with cirrhosis the serum levels of proinsulin and immunoreactive insulin were significantly higher in the fasting state and after glucose loading than in the healthy subjects. The serum level of true insulin was also higher in the patients with cirrhosis, but the difference was less pronounced and only significant at a few of the time points. The serum level of C-peptide was very similar in both groups. These results emphasize that cirrhosis is a condition in which the serum proinsulin level is raised and that this hyperproinsulinaemia contributes greatly to the increased immunoreactive insulin levels observed in patients with this disease.