Age, Body Mass Index, and Waist-to-Hip Ratio Related Changes in Insulin Secretion and Insulin Sensitivity in Women with Polycystic Ovary Syndrome: Minimal Model Analyses.

Insulin resistance is believed to be an integral component of the polycystic ovary syndrome (PCOS). Beta (ß) cell dysfunction is also found in PCOS. In the study, we determined the influence of age, body mass index (BMI), and waist-to-hip ratio (WHR) on insulin response to oral glucose load (OGTT) and on insulin sensitivity (Si) and ß-cell function in young women with PCOS. One hundred fourteen patients with PCOS and 41 controls with normal basal plasma glucose were studied. A 75-g OGTT was performed to determine glucose tolerance and insulin response. Insulin sensitivity and ß-cell function were studied using a modified frequently sampled IV glucose tolerance test (FISGTT) to determine the acute insulin response (AIRG), as well as Si by minimal model analysis. Si was decreased in PCOS women (2.49 0.18 vs. 3.41 ± 0.36, p < 0.05), but no difference in AIRG existed between the PCOS and control group (75.1 ± 4.6 vs. 63.4 ± 4.6, p < 0.05). BMI and WHR correlated negatively with Si (r = -0.43; r = -0.289, p < 0.001, respectively), but not with AIRG (r = 0.116; r = -0.02, p > 0.05, respectively). Increasing age correlated negatively with AIRG (r = -0.285, p < 0.001). There was a significant interaction between disease (PCOS), BMI, and WHR on Si as well as between age and PCOS on AIRG. Thus, patients below the age of 25 with PCOS showed enhanced AIRG (89.5 ± 7.1 vs. 65.1 ± 6.7, p < 0.05) and decreased Si (2.43 ± 0.25 vs. 4.52 ± 0.62, p < 0.05) compared to age-matched controls. In conclusion, these data suggest that not all patients with PCOS have basal and stimulated hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Based on these data in young PCOS subjects, the development of insulin resistance and T2DM may be prevented with appropriate treatment strategies.

Therapeutic improvement of glucoregulation in newly diagnosed type 2 diabetes patients is associated with a reduction of IL-17 levels.

We explored the effect of therapeutic glucoregulation on the blood levels of proinflammatory T helper (Th)17 cytokines interleukin (IL)-17 and IL-23, and Th1 cytokines interferon (IFN)-γ and IL-12 in newly diagnosed type 2 diabetes patients. The investigated group consisted of 23 subjects (17 men and 6 women, age 26-64). The cytokine serum levels, glycated hemoglobin (HbA1c) as a marker of glucoregulation, homeostasis model assessment index as a measure of insulin resistance (HOMA-IR), and body mass index (BMI) were determined before and after 12 weeks of therapy consisting of standard lifestyle modification and metformin (1000 mg b.i.d.). The levels of Th17 and Th1 cytokines before treatment did not correlate with age, BMI or HOMA-IR. The patients with poor glucoregulation (HbA1c>7%, n=12), compared to those with good glucoregulation (HbA1c≤7%, n=11), had higher serum levels of Th17 and Th1 cytokines, but only the differences in IL-17 (median 21.2 pg/ml vs. 4.8 pg/ml) and IFN-γ 5 (0.6 pg/ml vs. 27.7 pg/ml) reached statistical significance (p=0.003 and p=0.012, respectively). The reduction of HbA1c values (from 8.6 to 5.9%, p=0.000) observed upon treatment in patients with poor glucoregulation was associated with a significant decrease in the concentration of IL-17 (from 21.2 to 12.9 pg/ml, p=0.020), but not IFN-γ (50.6 vs. 52.3, p=0.349). These data indicate that therapeutic improvement of glucoregulation might contribute to a reduction of IL-17 levels in newly diagnosed type 2 diabetes patients.

[Sleep and metabolic disorders].

In the 20th century, the prevalence of obesity has been increasing worldwide at an alarming rate and it is followed by an increase in the diseases for which obesity is major risk factor, like metabolic syndrome, diabetes type 2 and hypertension. These facts has been resulting in explosion of investigation devoted to explanation of pathogenetic mechanisms of this serious social and medical problems with the main idea to find adequate way of prevention as well as of treatment. Together with the observed epidemy of obesity and Type 2 diabetes, it was found parallel tendency for sleep curtailment, that was confirmed in numerous epidemiological studies, that coincide with its beginning and progress with this two epidemies. This facts lead to investigations with the idea to try to explaine possible mechanisms of the association between sleep curtailment, obesity, type 2 diabetes, metabolic syndrome and polycistic ovary syndrome. Having in mind that insulin resistance is one of the fundamental pathogenetic mechanism in these disorders, numerous studies were done with the aim to explain association between sleep curtailment and insulin resistance in obesity, Type 2 diabetes, metabolic syndrome and polycistic ovary syndrome. It was demonstrated that sleep curtailment may affect energy homeostasis of human organism with the effects on body weight increase through three different ways: appetite increase, prolongation of time for food intake and through decrease of energy expenditure. There are several postulated mechanism for the effect of sleep curtailment on development of insulin resistance as well as for predisposition for Type 2 diabetes. Among possible mechanism are included: increase of sympathetic neuronal acitvity, decreased cerebral utilisation of glucose, increase in evening cortisol values, growth hormone increase and disorder of neuroendocrine control of appetite which increases the risk for getting the body weight. Metabolic systems are of particular interest in the discussion of possible mechanisms to account for elevated inflammatory mediators during sleep deprivation, particularly because of the contributory role of insulin resistance in the development of impaired vascular function and increased inflammation.

The effects of education with printed material on glycemic control in patients with diabetes type 2 treated with different therapeutic regimens.

BACKGROUND/AIM: Diabetes mellitus (DM) is considered to be an epidemic, chronic and progressive disease. The treatment of DM reqiures substantial effort from both the diabetes treatment team and a patient. Patient education is one of the treatment elements. The most efficacious form and content of education has not yet been established. However, every DM education must include introduction to a substantial number of facts about diabetes. The aim of our study was to estimate the levels of DM knowledge and glycemic control in Serbian patients with DM type 2 as well as to estimate the effects of education using printed material on the levels of glycemic control and knowledge about DM. Also, the effects of education on glycemic control and the level of knowledge in differently treated patients were estimated. METHODS: The patients with DM type 2 (n = 364), aged 40 to 65 years, from three regional health centers, were randomized for the study. After informed consent, patients filled out the questionnaire, and were checked for HbA1c and fasting blood glucose. Finally, booklet "Healthy lifestyle with diabetes mellitus type 2" was given to them. The same procedure was repeated after 3, 6 and 18 months. RESULTS: There was a significant improvement in HbA1c levels after 3 months (8.00 +/- 1.66% vs 9.06 +/- 2.23%, p < 0.01) and after 6 months (7.67 +/- 1.75% vs 9.06 +/- 2.23%, p < 0.01). There was no further improvement in HbA1c levels after 18 months (7.88 +/- 1.46% vs 7.67 +/- 1.75%, p > 0.05). There was a significant improvement in the average test score (percent of correct answers per test sheet) after three monts (64.6% vs 55.6%, p < 0.01). There were no further statistically significant changes in the general level of DM knowledge after 6 months (65.0 +/- 32.5% vs 64.5 +/- 33.7%, p > 0.05) and after 18 months (64.8 +/- 32.7 vs 64.5 +/- 33.7%, p > 0.05). There was a significant diffrence in educational intervention response in DM type 2 patients on different therapeutic regimens. CONCLUSION: Education with printed material led to improvement in glycemic control and level of DM knowledge in our patients. Education with printed material may be a useful adjunct to DM treatment and should be structured according to the treatment modality.

Pitfalls in diagnosing a small cystic insulinoma: a case report.

Insulinoma is a rare pancreatic endocrine tumour and is typically sporadic and solitary. Over 90% of all insulinomas are benign. Cystic insulinomas are also rare. It is not difficult to determine the site of such neoplasm, as cystic insulinomas are usually 4-10 cm in diameter. We present the case of a patient with a histologically confirmed cystic insulinoma diagnosed after approximately 10 years of hypoglycaemia symptoms. This case is unique because of the small size (2.2 cm) of the tumour. Endoscopic ultrasound (EUS) was useful for localizing this tumour.

Ghrelin and the enteroinsular axis in healthy men.

OBJECTIVE: Ghrelin, a potent stimulator of GH secretion, also acts as an orexigenic hormone. Plasma ghrelin levels rise before meals with postprandial reduction, suggesting that circulating levels of enteroinsular hormones might influence ghrelin secretion. AIM: The aim of this study was to evaluate the effects of ghrelin on enteroinsular hormones in healthy men. DESIGN: Three tests were performed on 3 different days in 6 healthy men: On the first day, saline was infused from 0-120 minutes followed by a ghrelin bolus (1 microg/kg) administration (Test 1); on the second experimental day, GHRH was administered at 0 min, and a ghrelin bolus was given at 120 min (Test 2); on the third experimental day, GHRP-6 was administered at 0 min, followed by a ghrelin bolus at 120 min (Test 3). Plasma glucose, insulin, proinsulin, C-Peptide Glucagone Like Peptide one (GLP-1) determined at 0, 15, 30, 60, 90, and 120 min of the test period. RESULTS: There was a significant increase in AUC glucose (526.41+/-22.91 mmol . ml(-1) . min vs. 566.37+/-15.64 mmol . ml(-1) . min; p<0.05) and AUC insulin (756.25+/-107.56 mU . ml(-1) . min vs. 981.62+/-180.32 mU . ml(-1) . min; p<0.05) and a significant decrease in AUC GLP-1 (2346.87+/-874.28 pmol . ml(-1) . min vs. 1769.5+/-784 pmol . ml(-1) . min; p<0.05) after ghrelin administration in Test 1 compared to Test 3. There was a mild but non-significant increase in AUC for insulin, proinsulin, and C-Peptide and a mild reduction in AUC GLP-1 after every ghrelin administration. CONCLUSION: There was no evidence of a direct effect of ghrelin administration on enteroinsular hormone levels in this study. However, ghrelin may potentiate the glucose-insulin stimulatory effects of GHRP-6. More studies should be carried out for further evaluation of ghrelin-enteroinsular hormones interplay.

[Use of continuous subcutaneous insulin infusion by a portable insulin pump during pregnancy in women with type 1 diabetes mellitus].

BACKGROUND/AIM: Diabetes mellitus is associated with an increased risk for neonatal morbidity and mortality. One of the most important goals in treating pregnancies complicated with diabetes is keeping glucose level within the normal range, especially in the first trimester. A portable insulin pump for continuous subcutaneous insulin infusion (CSII) represents the best form of therapy for patients with type 1 diabetes mellitus during pregnancy. The aim of our study was to evaluate the effects of therapy with a portable insulin pump for continuous subcutaneous insulin infusion during the first trimester of pregnancy on the quality of glycoregulation and pregnancy outcome in women with type 1 diabetes mellitus. METHODS: A total of 17 newly diagnosed pregnant women with type 1 diabetes mellitus were treated with CSII therapy for three months. The parameters of glycoregulation (hemoglobin A, glycosylated--HbAlc, mean blood glucose value in daily profiles--MBG, daily requirement for insulin--IJ/kg BM), lipid levels, blood preassure and renal function were estimated before and after the therapy. These parameters were correlated with parameters of pregnancy outcome: fetal weight, APGAR score, duration of pregnancy. RESULTS: There was a significant improvement in HbA1c (8.94 +/- 1.62 vs. 6.90 +/- 1.22 %,p < 0.05), MBG (9.23 +/- 2.22 vs. 6.41 +/- 1.72 mmol/l, p < 0.01), and daily requirement for insulin (0.66 +/- 0.22 vs. 0.55 +/- 0.13 IJ/kg BM, p < 0.05) during the CSII therapy. There were significant correlations between fetal weight and HbAlc (r = -0.60, p < 0.05), triglyceride levels (r = -0.63, p < 0.01), and the number of pregnancies (r = -0.62, p < 0.01), as well as between APGAR score and MBG (r = -0.52, p < 0.05) and cholesterol levels (r = -0.65, p < 0,01) before a portable insulin pump was applicated. CONCLUSIONS: There was a significant improvement in the quality of glycoregulation during CSII therapy in the pregnant women with type 1 diabetes mellitus. The quality of glycoregulation in the moment of conception was the important factor for pregnancy outcome.

Age and body mass related changes of cardiovascular risk factors in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is considered a metabolic disorder closely related to obesity, insulin resistance (IR), hyperinsulinemia and unfavorable lipid profile, all increasing the risk for the occurrence of cardiovascular diseases. The aim of this study was to assess age and body mass index (BMI) related changes of cardiovascular risk factors in 90 women with PCOS. The cut-off age point was 30 years and for BMI 27.8 kg/m2. In all patients systolic and diastolic blood pressure (BP), metabolic parameters comprising values of glucose and insulin during oral glucose tolerance test (OGTT), and basal lipid values were determined. Significant increase in blood pressure (BP) indices, basal insulin values and insulin resistance (IR) assessed by HOMA model were observed with aging and the increase of BMI, while the parameters of glucose metabolism, total cholesterol and triglycerides were significantly elevated only with aging. However, the correlation between the indices of arterial blood pressure, and lipid and glucose metabolism parameters occurred only in patients over 30 years of age, pointing to the causative relation and the consequent deterioration of IR and lipid profile with aging, influencing cardiovascular function in women with PCOS.