Metabolic determinants of NAFLD in adults with type 1 diabetes.

AIM: To assess the main metabolic determinants of non-alcoholic fatty liver disease (NAFLD) in adult patients with type 1 diabetes (T1D). METHODS: 115 patients with T1D were divided into 4 groups according to NAFLD grade. NAFLD was diagnosed via transient elastography when CAP > 233 dB/m. Body composition was evaluated by Inbody720, Biospace. Serum lipids, liver enzymes, uric acid, creatinine, hsCRP and HbA1c were evaluated at fasting. RESULTS: The overall prevalence of NAFLD was 47% (n = 54). In the subgroup with BMI > 25 kg/m2 NAFLD prevalence was 66%; and positive family history of type 2 diabetes brought the risk up to 76%. 37% of the lean individuals also had NAFLD. HbA1c > 7% doubled the risk of NAFLD. Waist circumference > 82.5 cm was independently related to NAFLD, accounting for 24% of its variation in females. Accumulation of two and three metabolic syndrome (MetS) components, besides hyperglycemia, increased the risk of NAFLD by 14% (p < 0.0001) and 6% (p = 0.024), respectively. Lean NAFLD correlated with total insulin dose; NAFLD in overweight T1D patients correlated with triglycerides. CONCLUSIONS: NAFLD is highly prevalent in adults with T1D and obesity or other metabolic derangements and might be independently related to poor long-term glycemic control and waist circumference in females.

A Case of Mody 2 - Associated Hyperglycemia Diagnosed as Gestational Diabetes.

Maturity-onset diabetes of the young (MODY) is the most common monogenic form of diabetes, accounting for 1-2% of all diabetes cases. At least 14 different MODY subtypes have been identified the most common of which is MODY 2 caused by mutations in the glucokinase (GSK) gene. The mild hyperglycemia of MODY 2 is often first detected during pregnancy. Patients with MODY are usually misdiagnosed as either idiopathic type 1 or type 2 diabetes. The recognition of MODY 2 during pregnancy has important clinical implications as the management of hyperglycemia may differ from the established algorithm in gestational diabetes. Fetus development could be seriously affected in case it has inherited the GSK mutation and maternal hyperglycemia is insulin treated to the pregnancy adopted glycemic targets. The case report describes the stepwise diagnostic approach to a 43-year-old woman with a history of gestational diabetes and persistent prediabetes who was found to be a carrier of a heterozygous pathogenic variant in GSK (c.184G>A) and discusses the possible genotype of her two children according to their birth weight.

Relationship between cardiac autonomic neuropathy and cardio-metabolic risk profile in adults with type 1 diabetes.

AIM: The present study aims to determine the prevalence and association of cardiac autonomic neuropathy (CAN) with some traditional cardio-metabolic risk factors in adults with type 1 diabetes (T1D). MATERIAL AND METHODS: 235 adults with T1D, divided into three groups according to diabetes duration, were recruited in this cross-sectional study from May 2017 till December 2018. Anthropometric parameters and blood pressure were measured. Lipids, liver enzymes, uric acid, creatinine, HbA1c and high sensitive C-reactive protein (hsCRP) were measured at fasting. Albumin/creatinine ratio (ACR) was measured in a first spot urine sample. Body composition was evaluated using bio-impedance analysis, Inbody720 (Biospace, USA). Advanced glycation end products (AGEs) were assessed by autofluorescence method, AGE Reader (Diagnoptics, The Netherlands). CAN was assessed by ANX-3.0 monitoring technology (ANSAR Medical Technologies, Inc., Philadelphia, PA), applying standard clinical tests. 2005 IDF and 2009 JIS definitions were used to define Metabolic Syndrome (MetS). RESULTS: The prevalence of CAN was 23% and increased with diabetes duration. Sympathetic activity was independently related to age, albumin/creatinine ratio (ACR) and total body fat mass, and parasympathetic activity - to age and ACR. Elevated hsCRP, AGEs and body fat, diabetic retinopathy and nephropathy, as well as hypertension, dyslipidemia and metabolic syndrome were found to increase the risk of CAN in T1D. CONCLUSION: CAN appears to be a common complication of T1D, especially with longer duration, and is found to be related to diabetic microvascular disease and metabolic syndrome components.

Epigenetic alterations in patients with type 2 diabetes mellitus.

Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of <5 years and (iv) of >5 years. The MBD2 expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in Prdx2 and SCARA3 genes, connected to oxidative stress protection and in BRCA1 and Tp53 tumor-suppressor genes. In conclusion, increased MBD2 expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of Prdx2 and SCARA3 genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of BRCA1 and Tp53 genes unraveled an epigenetic cause for T2DM related increase in cancer risk.

Regional differences in diabetic patients' pharmacotherapy in Bulgaria.

BACKGROUND: The regional analyses play an important role in understanding a state of diabetes mellitus management and to support informed policy options. They need to be explored in more details in order to ensure an equal patients' access to health care services of the same value and quality. AIM: The aim of this study is to analyze regional differences in a cost of diabetes therapy for insulin users in Bulgaria. MATERIALS AND METHODS: It is a combined prospective and retrospective observational study with duration of 6 months. Diabetic patients on insulin therapy were recruited by 35 endocrinologists. Information about the health care resources used was collected within 3-prospective and 3 retrospective months in 2010 and 2011. The regional cost of illness analysis was performed by calculating the average cost attributable to each individual patient despite the fact that some might not use a particular health care resource. Subgroup analysis was performed for hospitalized patients. RESULTS: A detailed analysis revealed cost differences in the regions, especially with more vulnerable population like Burgas and Pleven regions. Another reason for the cost differences is the type of insulin or type of therapy. Our study confirms the fact that the hospitalizations are the major cost driver. Rising diabetes prevalence and associated costs, including hospitalizations and management of diabetes complications, are a growing concern. The last possible reason for regional differences is the patients' characteristics and therapy differences. We add evidence demonstrating that the patients on insulin and OAD consume more resources including hospitalizations and suffer from more complications of diabetes. CONCLUSIONS: Reasons for regional differences might have different origin as there are various population characteristics, type of therapy, socio economic status and others.

Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study.

AIMS: To investigate efficacy and safety of dual therapy with liraglutide and metformin in comparison to glimepiride and metformin, and metformin monotherapy over 2 years in patients with type 2 diabetes. METHODS: In the 26-week the Liraglutide Effect and Action in Diabetes (LEAD)-2 core trial, patients (n = 1091) were randomized (2 : 2 : 2 : 1: 2) to liraglutide (0.6, 1.2 or 1.8 mg once-daily), placebo or glimepiride; all with metformin. Patients were enrolled if they were 18-80 years old with HbA1c 7.0-11.0% (previous monotherapy ≥3 months), or 7.0-10.0% (previous combination therapy ≥3 months), and body mass index ≤40 kg/m(2) . Patients completing the 26-week double-blinded phase could enter an 18-month open-label extension. RESULTS: HbA1c decreased significantly with liraglutide (0.4% with 0.6 mg, 0.6% with 1.2 and 1.8 mg) versus 0.3% increase with metformin monotherapy (p < 0.0001). HbA1c decrease with liraglutide was non-inferior versus 0.5% decrease with glimepiride. Liraglutide groups experienced significant weight loss (2.1, 3.0 and 2.9 kg with 0.6, 1.2 and 1.8 mg, respectively) compared to weight gain (0.7 kg) with glimepiride (p < 0.0001). Weight loss with liraglutide 1.2 and 1.8 mg was significantly greater than with metformin monotherapy (1.8 kg; p = 0.0185 and p = 0.0378 for 1.2 and 1.8 mg, respectively). The occurrence of minor hypoglycaemia was <5.0% in all liraglutide groups, significantly less than with glimepiride (24.0%; p < 0.0001). Liraglutide was well tolerated overall: gastrointestinal events were more common than with glimepiride or metformin monotherapy, but occurrence decreased with time. CONCLUSIONS: Liraglutide provided sustained glycaemic control over 2 years comparable to that provided by glimepiride. Liraglutide was well tolerated, and was associated with weight loss and a low rate of hypoglycaemia.

Treatment for diabetic mononeuropathy with alpha-lipoic acid.

Twenty-three diabetic patients -- 16 men and seven women (mean age: 50.7 +/- 17.4 years; mean duration of diabetes: 13.6 +/- 6.9 years) -- with diabetic mononeuropathy of the cranial nerves participated in the study. Four of them were with mononeuropathia multiplex and total ophthalmoplegia, affecting the oculomotor, trochlear and abducent nerves; 12 with paresis of the oculomotor nerve, one -- of the trochlear nerve and six -- of the abducent nerve. They were treated with alpha-lipoic acid (600 mg) for 10 days daily intravenously, thereafter one film tablet of 600 mg daily for 60 days. On the 10th day, we found significant improvement in the clinical signs of diabetic mononeuropathy - double vision, motility and position of the eyeball, ptosis of the upper eyelid and mydriasis. The mean period of oral treatment was 69.1 +/- 23.8 days, following the 10-day intravenous application of alpha-lipoic acid, and full recovery of the diabetic mononeuropathy was achieved with this therapeutic approach. Peripheral neuropathy was present in 17 patients (74%). On the 10th day, we established a decrease in total symptom score by an average of 2.7 +/- 1.4 points and by the end of the treatment period it was improved by 5.9 +/- 1.9 points (p = 0.04). On the 10th day, we found a decrease of 33% in foot pain and by the end of the second month, it fell by 65.5% (p < 0.0001). Vibration perception threshold was reduced in these patients at entry -- mean: 2.42 +/- 1.8 at the great toe, 2.89 +/- 1.8 at the first metatarsal and 3.65 +/- 1.7 at the medial malleolus. By the end of the second month, it reached mean 4.7 +/- 1.8 (p < 0.002) at the great toe, 4.92 +/- 2.1 (p = 0.004) at the first metatarsal and 5.3 +/- 1.4 (p < 0.01) at the medial malleolus. Cardiovascular autonomic neuropathy was present in two of the patients and there was improvement after treatment in the Ewing's tests -- Valsalva manoeuvre, deep-breathing test and lying-to-standing test. The results of our study demonstrate that alpha-lipoic acid appears to be an effective drug in the treatment for not only peripheral and autonomic diabetic neuropathy, but also diabetic mononeuropathy of the cranial nerves leading to full recovery of the patients.

Gender-dependent effect of ageing on peripheral insulin action.

The aim of the present study was to investigate the effect of both gender and age on insulin secretion, peripheral insulin effectiveness and insulin-receptor binding. Eighty healthy volunteers, 40 females of mean age 38.47 +/- 11.37 years and mean BMI 21.99 +/- 2.06 kg/m(2) and 40 males of mean age 34.87 +/- 11.22 years and mean BMI 22.65 +/- 2.31 kg/m(2), with normal glucose tolerance participated in the study. Peripheral insulin effectiveness was measured by the artificial endocrine pancreas, using the euglycaemic hyperinsulinaemic clamp technique and insulin-receptor binding on circulating mononuclear blood cells. Peripheral insulin sensitivity was significantly higher in females as compared to males (p < 0.001), while males demonstrated higher total number of insulin receptors (p < 0.0001) and number of high-affinity receptors (p < 0.01). Peripheral insulin sensitivity decreased with ageing in both males and females, the reduction in females being more pronounced (p < 0.05). In the group under 40 years, the females demonstrated significantly higher insulin sensitivity as compared to males (p < 0.001) and lower insulin-receptor binding. Over 40 years, females presented higher peripheral insulin sensitivity and higher insulin-receptor binding. The percentage of specifically bound insulin increased significantly with ageing in females and decreased in males. We consider that probably the higher androgen level in males affects the post-receptor processes in insulin action and despite the higher insulin-receptor binding, males have lower insulin sensitivity. The androgen levels in females increase with ageing, which could probably affect peripheral insulin sensitivity at the post-receptor level. In conclusion, our results demonstrate that when analysing peripheral insulin effectiveness and insulin-receptor binding, one should always consider both gender and age.

The effect of smoking on peripheral insulin sensitivity and plasma endothelin level.

OBJECTIVES: The aim of the present study was to investigate the effect of smoking on peripheral insulin effectiveness. METHODS: Seven healthy volunteers, nonsmokers, of mean age 39.6 +/- 7.1 Years and mean BMI 22.65 +/- 11.98 kg/m2, without family history of diabetes mellitus, with normal blood pressure participated in the study. All the parameters were studied twice - at baseline as well as after smoking (4 cigarettes per one hour). The study was performed in three days: at the first day we studied peripheral insulin effectiveness (M) in vivo by the artificial endocrine pancreas (Biostator), using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding on circulating mononuclear blood cells; at the second day - the same parameters after one-hour smoking during the third hour of clamping; at the third day - plasma endothelin level, blood pressure and heart rate at baseline and after one-hour smoking. RESULTS: There was a significant decrease in glucose utilization during the second clamp test, when the volunteers smoked during the third hour as compared to the test at baseline (p=0.04). This was accompanied by a significant decrease in insulin receptor affinity (p=0.04). Systolic blood pressure and heart rate increased significantly after one-hour smoking (p=0.03 and p=0.001, respectively). Plasma endothelin level increased significantly after smoking (from 0.62 +/- 0.15 pg/ml to 2.05 +/- 1.67 pg/ml, p=0.03). CONCLUSION: Our results demonstrate that smoking decreases peripheral insulin sensitivity reducing insulin receptor affinity. We have confirmed that smoking increases plasma endothelin level, which probably by causing vasoconstriction and consequent tIssue hypoxaemia could decrease peripheral glucose utilization. We consider that smoking could also have a direct effect on insulin receptor affinity, thus leading to decreased peripheral insulin effectiveness.

Sibutramine in the treatment of obesity in type 2 diabetic patients and in nondiabetic subjects.

Obesity is considered a chronic disease requiring treatment. The effect of sibutramine combined with hypocaloric diet and exercise on body weight, body fat mass, lipids, glycemic control, insulin secretion and insulin resistance was evaluated in a randomized, controlled, open-label study. A total of 44 obese type 2 diabetic patients (aged 45.2+/-5.2 years, BMI 33.62+/-2.2 kg/m(2)) and 49 obese nondiabetic subjects (aged 41.9+/-5.7 years, BMI 34.3+/-2.6 kg/m(2)) were treated with sibutramine for 3 months. Moreover, 39 age-matched obese type 2 diabetic patients and 41 obese nondiabetic subjects only on hypocaloric diet and exercise served as control groups. Insulin secretion was estimated during intravenous glucose tolerance test; insulin resistance was assessed by the HOMA index. There was a significant reduction in body weight in both sibutramine-treated diabetic patients (7.1%) and nondiabetic subjects (9.1%), accompanied by a significant reduction in body fat mass. HbA1c decreased significantly in the diabetic patients after sibutramine treatment. There was a significant improvement of lipid parameters in the two groups. Insulin resistance decreased by 21.9% in the sibutramine-treated diabetic patients and by 38.5% in the nondiabetic group. Weight loss was accompanied by an increase of 43.8% in first phase insulin secretion in the sibutramine-treated diabetic group; in the treated nondiabetic subjects there was a decrease in first and second phase insulin secretion and the area under the curve for total insulin secretion. In conclusion, sibutramine leads to a significant reduction in body weight, body fat mass and waist and hip circumferences; it improves insulin sensitivity, insulin secretion, glycaemic control and lipid parameters in both diabetic and nondiabetic obese subjects.

Insulin secretion, peripheral insulin sensitivity and insulin-receptor binding in subjects with different degrees of obesity.

OBJECTIVES: The aim of the present study was to investigate insulin secretion, insulin-receptor binding and peripheral insulin sensitivity in subjects with different degrees of obesity. METHODS: 36 obese subjects with normal glucose tolerance and different degrees of obesity and 40 healthy normal-weight subjects participated in the study. Peripheral insulin sensitivity was measured by using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding-on circulating mononuclear blood cells. Insulin secretion was studied during intravenous tolbutamide test. RESULTS: The subjects with I degree of obesity demonstrated a significant decrease in the number of total (p<0.0001) and high-affinity (p<0.01) insulin receptors per cell, as well as significantly higher insulin receptor affinity (p<0.01) as compared to the normal-weight subjects. The subjects with II degree of obesity also demonstrated a significant decrease in the number of total (p<0.0001) and high-affinity receptors (p<0.001) per cell as well as an increase (p<0.001) in insulin-receptor affinity as compared to the controls. The significantly decreased receptor number in the subjects with I and II degree of obesity was accompanied by an increase in insulin receptor affinity; thus their insulin-receptor binding being maintained similar to the controls. The subjects with III degree obesity presented a significant decrease (p<0.0001) in the number of both the total and high-affinity insulin receptors as well as a reduction in insulin receptor affinity as compared to the controls. Therefore the percentage of specifically bound insulin was significantly lower (p<0.01) as compared to that of the control group. Insulin resistance in the obese subjects is associated with secondary hyperinsulinaemia, which is present in subjects with I and II degree of obesity; while in severely obese subjects exhaustion of beta-cell secretory capacity is observed. CONCLUSION: We consider that III degree of obesity appears to be a risk factor for type 2 diabetes mellitus as the alterations in insulin sensitivity, insulin-receptor binding and beta-cell secretion are quite similar to the reported in diabetic patients.

The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients.

The aim of this study was to evaluate the effect of vitamin D3 supplementation on insulin secretion and insulin resistance. Ten females with type 2 diabetes being treated with oral hypoglycaemic agents and with normal serum and urine calcium levels were enrolled in the study. The study was conducted in March, when levels of vitamin D are lowest in our region. The level of plasma 25(OH)D was measured (normal range in winter 25-120 nmol/l). The first (FPIS) and second (SPIS) phases of insulin secretion were studied during IVGTT. Peripheral insulin resistance was measured. A group of 17 age- and BMI-matched females with normal glucose tolerance served as a control group. The diabetic patients were treated with cholecalciferol 1332 IU daily for one month. The mean plasma 25(OH)D level was 35.3 +/- 15.1 nmol/l at baseline, 70% of patients being vitamin D deficient. After one month of treatment with vitamin D3, the plasma 25(OH)D level increased by a mean of 75.8%; 70% of the patients achieved normal vitamin D levels. FPIS increased significantly by 34.3%, while the change in SPIS of 20.4% was not significant (p > 0.8). We found a significant correlation between the change in FPIS and the change in 25(OH)D level after vitamin D3 supplementation (p < 0.018). The results showed a decrease of 21.4% in insulin resistance after one month, but the change was not significant. Bearing in mind that the main defects in type 2 diabetes mellitus are reduced FPIS and insulin resistance, and the favourable effect vitamin D3 had on them, we suggest vitamin D3 deficiency may at least partly contribute to the impairment of insulin secretion and probably of insulin action. Our results suggest that vitamin D3 supplementation could be an element in the complex treatment of type 2 diabetes mellitus during the winter.

Therapeutic approach in insulin resistance with acanthosis nigricans.

The aim of the present study was to evaluate the effect of metformin in very obese subjects with acanthosis nigricans. Five patients (two obese children, mean age 14.4 +/- 0.6 yr, mean BMI 35.2 +/- 1.9 kg/m2 and normal glucose tolerance, and three newly diagnosed obese type 2 diabetic patients, mean age 37.7 +/- 3.2 yr, mean BMI 37.7 +/- 2.9 kg/m2) were enrolled in the study Insulin secretion was measured during oral glucose tolerance (OGT) and intravenous glucose tolerance (IVGT) tests. Insulin resistance was assessed by the homoeostasis model assessment (HOMA) index. All the patients were treated with metformin at a mean daily dose of 2.23 +/- 0.45 g. Six months after initiation of therapy we found a significant reduction in AUC for insulin secretion during OGTT (p < 0.05), due to reduction in both basal and stimulated insulin secretion (p<0.05). Body weight was reduced by mean 4.7 +/- 1.9% and body fat mass by 8.95 +/- 3.7%. We have demonstrated a significant decrease of 36.3% in insulin resistance (p < 0.01). Our results demonstrate that metformin reduces hyperinsulinaemia, body weight and fat mass and improves insulin sensitivity in patients with insulin resistance and acanthosis nigricans.

Effects of paracetamol and propacetamol on gastric mucosal damage and gastric lipid peroxidation caused by acetylsalicylic acid (ASA) in rats.

We have studied the effect of paracetamol and its pro-drug propacetamol on gastric mucosal damage induced by acetylsalicylic acid (ASA) and its possible relation to changes in gastric lipid peroxidation status in rats. Paracetamol or propacetamol were administered intragastrically 1h before ASA (300 mg kg(-1)) in the following equivalent doses: 62.5, 125.0 and 250.0 mg kg(-1) or 125.0, 250.0 and 500.0 mg kg(-1), respectively. The effects of the tested agents were compared to that of prostaglandin E2 (PGE2) 15, 30 and 60 mg kg(-1). Gastric ulcer formation was estimated morphometrically 4h after ASA administration. Malondialdehyde (MDA), glutathione (reduced, GSH, and oxidized, GSSG) and uric acid (UA) were determined in gastric mucosa and blood plasma and used as biochemical markers of the oxidative status. The results showed that paracetamol (250, 125, 62.5 mg kg(-1)) and propacetamol (500, 250, 125 mg kg(-1)) diminished the area of ASA-induced gastric lesions. The effect of propacetamol was more pronounced than that of paracetamol and similar to that of PGE2. Gastric MDA increased 3-fold in the ASA-group. The tested agents reduced it by a range of 30-70%. In all pretreated groups gastric glutathione and UA levels were found higher than that of control group and lower than that of ASA-group. Paracetamol and propacetamol, as well as PGE2, diminished the lipid peroxidation in plasma to a lesser extent than in gastric mucosa, but maintained elevated levels of the selective plasma antioxidant UA. These results show that the ASA-induced gastric mucosal damage is accompanied by the development of oxidative stress, evidenced by the accumulation of MDA, and concomitant initial activation of cell antioxidant defences. As paracetamol and propacetamol tend to decrease gastric lesions caused by ASA and alter gastric mucosal MDA, glutathione and UA values in a favorable manner, it could be suggested that their effects on the gastric mucosa could be related to interference with oxidative stress development.

Effect of hormone replacement therapy on insulin secretion and insulin sensitivity in postmenopausal diabetic women.

The aim of the present study was to evaluate the effect of three different combinations of hormone replacement therapy (HRT) on insulin secretion, peripheral insulin sensitivity, serum lipid levels and parameters of oxidative stress. Seven type II diabetic women of mean age 55.4 +/- 4.7 years, who had been menopausal for an average of 5 years, were enrolled in the study. Phases of insulin secretion--first (FPIS) and second (SPIS)--and the area under the curve (AUC) for insulin secretion were studied during an intravenous glucose tolerance test (IVGTT). Insulin sensitivity was determined using the manual euglycemic-hyperinsulinemic clamp technique. Three different HRT combinations were applied consecutively for 3-month periods: estradiol valerate plus cyproterone acetate (Climen); transdermal 17 beta-estradiol (System TTS 50) plus dydrogesterone (Duphaston) 10 mg daily for 10 days a month; oral 17 beta-estradiol plus dydrogesterone (Femoston) for 14 days a month. A group of nine women with normal glucose tolerance (according to World Health Organization criteria during a 75-g oral glucose tolerance test (OGTT)), of mean age 50.1 +/- 8.2 years and mean body mass index 24.60 +/- 2.01 kg/m2, were also studied, and served as a control group. Insulin secretion improved significantly after Climen: FPIS increased by 16% and SPIS by 44%. Insulin sensitivity increased by 50% after Systen TTS 50 + Duphaston; fasting hyperinsulinemia was normalized and total antioxidant capacity of the serum (TAOCS) was significantly raised (p < 0.01). Femoston led to an increase in insulin sensitivity (by 23%) and in TAOCS (p < 0.05), while fasting hyperinsulinemia remained unchanged. HRT should be prescribed in type II diabetic postmenopausal women because of its favorable effect on existing pathophysiological defects. Cyproterone acetate should be preferred in cases with a predominant beta-cell insulin secretion defect, while dydrogesterone in combination with a transdermal estrogen should be recommended in cases with leading insulin resistance.

Insulin secretion and anti-GAD65 antibodies in subjects with impaired glucose tolerance.

The study was designed to evaluate the pattern of insulin secretion and the presence of anti-GAD65 antibodies as beta-cell autoimmune marker in subjects with impaired glucose tolerance (IGT) and their impact on the further development of glucose intolerance. 29 subjects with IGT, of mean BMI 24.7 +/- 2.4 kg/m(2) and mean age 37.7 +/- 7.0 years were enrolled in the study. They were followed-up once yearly for three years. A group of 59 age- and weight-matched subjects with normal glucose tolerance (NGT) served as a control group. 42 newly-diagnosed diabetic patients, of mean BMI 24.4 +/- 2.7 kg/m(2) and mean age 37.2 +/- 6.9 years were also studied. According to their response during IVGTT the subjects with IGT were divided into two groups. The first group (n = 11)(IGT-I) showed reduced FPIS (34.0 +/- 8.9 mU/l vs 114.4 +/- 41.2, p < 0.001), SPIS being within normal values, and reduced AUC for total insulin secretion (1554.1 +/- 496.3 vs 2323.6 +/- 804.5 mU/l x 60 min, p < 0.001); the difference with type 1 diabetic patients being significant (p < 0.001), the pattern of insulin secretion being quite similar to that of type 2 diabetic patients. The other group (n = 18) (IGT-II) demonstrated normal insulin secretion (FPIS, SPIS, AUC for insulin secretion), not differing from that of the controls with NGT. Anti-GAD65 were present in 3.3% of subjects with NGT, in 73.7% of patients with type 1 diabetes and in none of type 2 diabetic patients. 18% from the group with IGT-I were anti-GAD65 positive, and 22% - from IGT-II. 5 of the subjects with IGT-I developed diabetes during the follow-up period - 2 at the 1st year, 1 at the 2nd year and 2 - at the third year. One of these patients was anti-GAD65 positive (having the highest anti-GAD65 level amongst the others with IGT - 15.2 U/ml), showing pattern of insulin secretion similar to that of type 1 diabetic patients. 3 of the subjects with IGT-II reverted to NGT within the first year and 2 - at the second year, none of them being anti-GAD65 positive. The anti-GAD65 positive patients from this group remained with IGT, and none progressed to diabetes mellitus. We consider that IVGTT allows precise assessment of the phases of insulin secretion and in combination with the study of anti-GAD65 antibodies helps to identify the subjects with IGT at risk of developing diabetes mellitus. As far as the decrease in the FPIS is considered it could be proposed that such subjects are assigned to certain protective measures - diet, physical activity and some drugs affecting postprandial glucose levels.

Education of diabetic patients--a one year experience.

201 insulin-treated diabetic patients were followed upto 6 months and 1 year after a 5-day structured teaching program. There was a significant increase in overall quality of life (score 51+/-5.7 after 1 year versus 41+/-6.1 before education, P<0.01), due to reduction in depression (P<0.01) and anxiety (P<0.001) and increase in well-being (P<0.05). The metabolic control improved significantly - HbA(1c) fell from 9.1+/-1.5 to 8.0+/-1.1 and 7.8+/-1.3% after 6 months and 1 year, respectively, P<0.05. The rate of severe hypoglycaemia decreased from 0.15 to 0.06cas/pat/year after 1 year (P<0.01). The incidence of diabetic ketoacidosis decreased from 0.30 to 0.14cas/pat/year (P<0.01). These results demonstrate that structured patient education improves the quality of life of diabetic patients and their metabolic control and significantly reduces the rate of acute complications.

Prostaglandin E2 affects both insulin secretion and peripheral insulin sensitivity.

The effect of prostaglandin E2 (PGE2) on plasma C-peptide (CP) level and peripheral insulin effectiveness was studied in twenty-five healthy volunteers. Plasma CP levels were studied in 14 volunteers (group C) during a three-hours PGE2 infusion. The same experiment was repeated a week later, with saline infusion. Plasma CP level were measured 15 minutes before the infusion, at the beginning of the experiment (0 min) as well as 15, 30, 60, 120 and 180 minutes after the start of the infusion. Peripheral insulin sensitivity was studied in vivo by means of the artificial endocrine pancreas (Biostator), using the euglycaemic hyperinsulinaemic clamp technique. The healthy volunteers underwent a three-hour experiment with saline (group A) or with saline and PGE2-10 micrograms/min during the third hour of clamping (group B). There was a significant decrease in plasma CP level at the 15 th and 30 th minute of PGE2 infusion in the subjects from group C (p less than 0.05). In the group A there was an increase of 14.2% in the amount of glucose infused during the third hour of clamping as compared to the second (2nd-9.673 +/- 1.680 mg/kg/min, 3rd-11.051 +/- 1.802 mg/kg/min). The amount of glucose infused in the subjects of group B remained the same in the course of clamping (2nd hour-7.938 +/- 2.180 mg/kg/min, 3rd hour-7.932 +/- 2.284 mg/kg/min). The difference in the dynamic changes of the amount of glucose infused between the two groups of volunteers (group A and group B) was significant (F = 5.68, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)