Efficacy of benfluorex in combination with sulfonylurea in type 2 diabetic patients: an 18 to 34-week, open-label, extension period.

AIM: The aim of this trial was to obtain further data on the efficacy and safety of benfluorex as an add-on therapy in type 2 diabetic patients insufficiently controlled by sulfonylurea monotherapy who had a limitation for the use of metformin during a 4-month extension period following a 4-month double-blind trial. METHODS: Patients who completed the 18-week double-blind period entered the 16-week extension period. Patients in the benfluorex group during the double-blind period continued benfluorex 450 mg/day (B-B group), whilst patients in the placebo group switched to benfluorex 450 mg/day (P-B group). The main efficacy criterion was HbA(1c), analyzed as the change from week 18 (W18) to the end of treatment using a two-sided Student paired t-test. Secondary criteria were fasting plasma glucose (FPG), insulin resistance and lipids. RESULTS: Between W18 and the end of treatment, HbA(1c) decreased in the P-B group from 8.53+/-1.37% to 7.49+/-1.04% (P<0.001) and remained stable in the B-B group from 7.52+/-1.07% to 7.53+/-1.14% (NS). In the P-B group, parameters of glycemic control showed improvements from W18 to week 34 (W34) which were similar to those observed from baseline to W18 in the B-B group. Overall, the target HbA(1c) (

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.

Alpha-lipoic acid in the treatment of autonomic diabetic neuropathy (controlled, randomized, open-label study).

AIM: to evaluate the effect of alpha-lipoic acid in autonomic diabetic neuropathy in a controlled, randomized, open-label study. MATERIAL AND METHODS: 46 patients with type 1 diabetes and different forms of autonomic neuropathy, of mean age 38.1 +/- 12.5 years and mean duration of diabetes 16.8 +/- 8.9 years were treated with alpha-lipoic acid for 10 days 600mg daily iv, thereafter one film tablet of 600mg daily for 50 days. 29 type 1 diabetic patients with autonomic diabetic neuropathy, of mean age 40.2 +/- 9.3 years and mean duration of diabetes 15.4 +/- 7.9 years served as a control group. We have followed-up patients' complaints, Ewing's tests, laboratory parameters of oxidative stress. RESULTS: There was a significant improvement after treatment in the score for severity of cardiovascular autonomic neuropathy--from 6.43 +/- 0.9 to 4.24 +/- 1.8 (p<0.001), while in the control group it worsened from 6.18 +/- 1.3 to 6.52 +/- 0.9 (p>0.1). We found improvement in the Valsalva manoeuvre after treatment - from 1.05 +/- 0.04 to 1.13 +/- 0.08 (p<0.001); in the deep-breathing test -from 3.4 +/- 2.8 to 10.4 +/- 5.7 (p<0.001); and in the lying-to-standing test--from 0.99 +/- 0.01 to 1.01 +/- 0.02 (p>0.1), while in the control group there was no improvement. There was a beneficial effect of treatment on the change of systolic blood pressure at the lying-to-standing test--from 22.7 +/- 11.5 to 9.8 +/- 7.9 (p<0.001), while in the control group the change was 20.5 +/- 11.1 mmHg and 19.7 +/- 12.9 mmHg (p>0.1), respectively. We found improvement in diabetic enteropathy in six patients; in the complaints of dizziness, instability upon standing in six patients; in neuropathic edema of the lower extremities in four patients and in erectile dysfunction in four patients after treatment, while in the control group no change was reported in the symptoms and signs of autonomic neuropathy by the end of the follow-up period. There were changes in the laboratory parameters of oxidative stress after therapy--total serum antioxidant capacity increased from 20.42 +/- 1.8 to 22.96 +/- 2.3 microgH2O2/ml/min (p<0.05), serum SOD activity - from 269.8 +/- 31.1 to 319.8 +/- 29.IU/l (p=0.02) and erythrocyte SOD--from 0.89 +/- 0.10 to 1.11 +/- 0.09 U/gHb (p=0.04). CONCLUSION: Our results demonstrate that alpha-lipoic acid (Thiogamma) appears to be an effective drug in the treatment of the different forms of autonomic diabetic neuropathy.

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.

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.

[Cyproterone acetate improves beta-cell function in postmenopausal women with diabetes mellitus type 2]. / Cyproterone acetate podobriava beta-kletuchnata funktsiia pri postmenopauzalni zheni sus zakharen diabet tip 2

Menopause is associated with two main risk factors for the development of type 2 diabetes mellitus--impaired beta-cell insulin secretion and insulin resistance. Physiologically estrogens improve carbohydrate metabolism, but this is not the case with different progestogens. The aim of the present study was to evaluate the effect of Cyproterone acetate (a progestogen with antiandrogenic activity) on insulin secretion, peripheral insulin sensitivity, lipid parameters and parameters of oxidative stress. Seven type 2 diabetic females, of mean age 55.4 +/- 4.7 years and mean BMI 30.8 +/- 9.39 kg/m2, in menopause for average 5 years, in good borderline glycaemic control (mean HbAic 7.8%), with dyslipidaemia, normal parameters of calcium and phosphate metabolism and with osteopenia (T-score < 88%) were enrolled in the study. They were treated with Estradiol valerate + Cyproterone acetate (Climen, Schering) for three months. Phases of insulin secretion--first phase (FPIS), second phase (SPIS) and AUC for FPIS and SPIS were assessed during IVGTT. Insulin sensitivity was determined with the manual method of euglycaemic hyperinsulinaemic clamp technique. The postmenopausal diabetic women in the present study were with overweight and obesity; they did not increase their body weight during HRT and even decreased it by mean 0.7%. Insulin secretion improved after Climen--FPIS increased by 16% and SPIS by 44%. Insulin sensitivity increased by 15%; triglycerides decreased by 16% and HDL-cholesterol increased by 27%. Total antioxidant capacity of the serum (TAOK) increased by 7%. The favourable effect on the pathophysiological mechanisms improved metabolic control--HbAic was reduced by mean 3% after 3 months. In conclusion, our results suggest that HRT with the progestogen Cyproterone acetate (Climen) should be preferred in postmenopausal type 2 diabetic females with predominant beta-cell insulin secretion defect.

Metformin in the treatment of obesity in subjects with normal glucose tolerance.

The aim of the present study was to evaluate the effect of metformin on body weight, body fat mass, waist circumference, lipid parameters, insulin secretion and insulin resistance in obese subjects with normal glucose tolerance. 26 subjects (16 females and 10 males), mean age 37.3+/-9.7 years and mean BMI 32.3+/-9.1kg/m2 were treated with individual hypocaloric diet and metformin at a mean dose of 2.38+/-0.32g for six months. Insulin secretion was studied during OGTT; insulin resistance was assessed by the HOMA index. We have found a reduction of 3.24% in body weight, which was accompanied by a decrease in body fat mass (by 7.45%, p<0.01) and in waist circumference (p<0.01). Insulin resistance decreased by 14.5% (p=0.02) after metformin. There was a significant decrease in the AUC for the total (by 17.6%, from 6999+/-1453 to 5763+/-1511mU/L.120min, p<0.01) and stimulated insulin secretion (by 17.1%, from 4215+/-1011 to 3495+/-925mU/L.120min, p=0.01) during OGTT after six-month treatment with metformin. In conclusion, the results from the present study demonstrate that metformin contributes to a reduction in body weight, body fat mass and waist circumference, improves insulin sensitivity and decreases basal, total and stimulated insulin secretion in obese subjects. Thus metformin appears to be an effective and well-tolerated drug in the treatment of obesity in subjects with normal glucose tolerance.

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.

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.

[Consensus on the treatment of type 2 diabetes mellitus]. / Konsensus otnosno lechenieto na zakharen diabet-tip 2.

The outcome data from the United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive drug treatment of diabetes mellitus-type 2 and the tight control of glycaemia and blood pressure are associated with lower incidence of chronic diabetic complications and mortality. The economical analysis showed out that money invested in the intensive drug treatment of diabetes and arterial hypertension resulted in less expenses for the treatment of diabetic complications. These data are the reason to suggest an algorythm for the treatment of diabetes mellitus type 2. The main aims are to achieve fasting blood glucose < or = 6 mmol/l, 2 hour postprandial glucose < or = 8 mmol/l and glycated haemoglobin (HbA1c) < or = 7.0%. The steps in the treatment include: non-pharmacological treatment, monotherapy with an oral drug, combined oral treatment, insulin therapy, combined insulin and an oral drug therapy. The blood pressure control aims to achieve a figure below 140/85 mm Hg, using monotherapy or a combination of antihypertensive drugs from different pharmacological groups.

Effect of growth hormone releasing hormone on growth hormone, prostaglandin E2 and insulin in non-insulin-dependent diabetic patients.

In a previous paper we demonstrated a link between growth hormone releasing hormone (GHRH) and prostaglandin E2 (PGE2) in their action on growth hormone (GH) in normal subjects. However, in diabetes mellitus various disturbances of GH and PGE2 secretion have been reported. In the present study the response of GH, PGE2 and insulin to GHRH (1 microgram/kg b.w.) intravenously was investigated in 12 poorly controlled non-insulin-dependent diabetic patients (8 males and 4 females) and 10 normal volunteers (5 males and 5 females). After GHRH injection, GH increased in diabetic patients from 2.28 +/- 0.52 mU/l to 14.76 +/- 1.29 mU/l at 30 min (p < 0.001). This response was not statistically different compared to the control subjects. The basal values of plasma PGE2 were significantly lower in diabetic patients than in control subjects. GHRH induced a slight but significant increase of PGE2 in normal subjects (9.80 +/- 0.44 pg/ml at 0 min; 14.50 +/- 1.30 pg/ml at 90 min, p < 0.05) and did not have any effect on PGE2 in diabetic patients. Serum insulin decreased significantly after GHRH in both normal subjects and diabetic patients at 60 min. We conclude that GH response to GHRH is not significantly impaired in poorly controlled non-insulin-dependent diabetic patients. The lack of an effect of GHRH on PGE2 in diabetic subjects provides further evidence of abnormal PGE2 synthesis or metabolism in this disorder. The physiological significance of the GHRH suppressive effect on serum insulin remains to be explained.

Improvement of lipoprotein lipid composition in type II diabetic patients with concomitant hyperlipoproteinemia by acipimox treatment. Results of a multicenter trial.

OBJECTIVE: To study the tolerability and efficacy of acipimox on hyperlipidemia and diabetes compensation in patients with NIDDM under conditions of a routine clinical practice. RESEARCH DESIGN AND METHODS: We recruited 121 patients (60 men and 61 women) from 10 participating clinical centers. They were randomly divided into two groups and treated for 3 mo either with acipimox (250 mg three times a day) or placebo, using an open study design. RESULTS: Acipimox treatment led to a significant drop in fasting serum total triglyceride levels (by 28%) after 1 mo of drug administration. This decrease prevailed up to the end of the 3-mo study. Serum total cholesterol levels declined by 14%, and high-density lipoprotein tended to rise in acipimox-treated patients. These changes in lipid metabolism were not accompanied by any adverse effects of acipimox on glucose metabolism as judged by HbA1c measurements and the oral glucose tolerance test. Eight patients (out of 82 treated with acipimox) reported moderate adverse events of transient character, such as skin reactions and gastric disturbances. CONCLUSIONS: Acipimox seems to be a useful agent for treatment of diabetic dyslipidemia and does not deteriorate glycemic control.

Factors for development of secondary failure to sulfonylurea drugs in non-insulin-dependent diabetes mellitus.

Thirty-five non-insulin-dependent diabetic subjects were divided into two groups, according to therapeutical approach. The first group consisted of 17 diabetics receiving sulfonylureas and maintaining a satisfactory metabolic control. The second group included 18 patients who were transferred from sulfonylureas to insulin treatment, i.e. patients developing secondary failure to sulfonylurea drugs. We established that the patients with secondary failure to sulfonylurea drugs show a significantly lower B-cell secretory response following stimulation with i.v. tolbutamide, a significantly lower peripheral insulin sensitivity by euglycemic hyperinsulinemic clamp, and an increased frequency of HLAB21 and HLADR1 antigens. This latter study was performed in 42 patients. We thus conclude that in these patients diabetes mellitus may be considered as a separate form of the disease, which needs reevaluation of the criteria concerning therapeutical approach, prognosis, and evolution.

[The phenotypic characteristics and incidence of dyslipoproteinemias in diabetic patients]. / Fenotipicheskaia kharakteristika i chastota dislipoproteidemii u bol'nykh sakharnym diabetom.

A total of 121 inpatients with insulin and noninsulin dependent diabetes mellitus were investigated. The patients with noninsulin dependent diabetes mellitus were divided into 2 groups with relation to the presence or absence of secondary resistance to sulfonyl urea derivatives. Changes in the plasma and lipoprotein concentration of cholesterol (ChS) and triglycerides (TG) were analyzed. According to the author's classification, changes in lipoprotein patterns were distributed in some phenotypes of dyslipoproteinemias (DLP) and their prevalence was studied among the examinees. DLPs were detected in 84.3% of the patients (59.8% were latent). The patients demonstrated a high frequency of hypocholesterolemia of very low density lipoproteins (57.8%) and hypertriglyceridemia of low density lipoproteins (31.4%). These intralipoprotein variations were shown to be the chief element of phenotypical characterization of II (c, d), IV (b, c) and VI (a, b, c) DLP types, not included in Fredrickson's classification.

[Catecholamine excretion in insulin-treated diabetic patients]. / Katecholaminausscheidung bei insulinbehandelten Diabetikern.

The urine excretion of the catecholamines adrenalin, noradrenalin and dopamine as well as the serum levels of cortisol and STH were determined with the aim to establish objective criteria for a "latent" hypoglycaemia in diabetics. The altogether 45 insulin-requiring diabetics had no hypoglycaemia (n = 28) and the decrease of blood sugar, respectively, occurred during the daytime (n = 6) or at night (n = 11). From the results no significance for the catecholamines as parameters of a hypoglycaemia that happened long ago can be derived. Deviation in the circadian rhythms of the cortisol levels in diabetics with hypoglycaemias need the securing by further investigations.

[High-degree obesity--a risk factor for the development of diabetes mellitus]. / Visokostepennoto zatlustiavane--riskov faktor za razvitie na zakharna bolest.

In high degree obesity there a significantly smaller area under the curve of C-peptide after stimulation with Tolbutamide and significantly lower insulin sensitivity measured in vivo by euglycemic hyperinsulinemic clamp-technique (Biostator) than in moderate obesity. This allows the conclusion that high degree obesity is a risk factor for the development of diabetes mellitus.