Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: impact of weight reduction.

BACKGROUND: Omentin-1 is an anti-inflammatory adipokine produced preferentially by visceral adipose tissue. Plasma levels of omentin-1 are decreased in obesity and other insulin-resistant states. Insulin resistance contributes to the changes of cholesterol synthesis and absorption as well. The aim of this study was to characterise omentin-1 plasma levels in obese patients with diabetes mellitus type 1 during weight reduction, and to elucidate the relationship between cholesterol metabolism and omentin-1. METHODS: Plasma levels of omentin-1 were measured in obese type 1 diabetics (n=14, body mass index >30 kg m(-2), age 29-62 years) by enzyme-linked immunosorbent assay (BioVendor). Gas chromatography with flame ionisation detector (Fisons Plc.,) was used to measure squalene and non-cholesterol sterols-markers of cholesterol synthesis and absorption (phase I). Measurements were repeated after 1 month (phase II; 1 week of fasting in the hospital setting and 3 weeks on a diet containing 150 g saccharides per day) and after 1 year (phase III) on a diet with 225 g saccharides per day. RESULTS: Omentin-1 plasma levels were stable during phases I and II, but significantly increased (P<0.001) during phase III. Omentin-1 plasma dynamics were significantly associated with plasma levels of high-density lipoprotein (P=0.005) and triacylglycerols (P=0.01), as well as with lathosterol (P=0.03). CONCLUSION: Omentin-1 plasma levels significantly increased during the weight reduction programme. Omentin-1 plasma dynamics suggest a close relationship with cholesterol metabolism.

Effects of body weight reduction on plasma leptin and adiponectin/leptin ratio in obese patients with type 1 diabetes mellitus.

The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) microg . l(-1) and transiently decreased immediately after fasting: 3.45 microg . l(-1) (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) . 10(3) and transiently increased immediately after fasting: 2.22 (1.26; 3.24) . 10(3), (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet.

[SAVOR TIMI 53 -  Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus]. / SAVOR-TIMI 53 - Vysledky saxagliptinu a kardiovaskularni vysledky u pacientu s diabetes mellitus 2. typu.

BACKGROUND: The type 2 Diabetes Mellitus treatment is currently effective but still not ideal. A therapy based on the incretins, which represents a significant qualitative progress, is close to an ideal. The first completed mortality study with dipeptidyl peptidase (DPP 4) inhibitors is the study called SAVOR as presented in Amsterdam during the European Cardiology Congress in 2013. METHODOLOGY: SAVOR (Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus) randomised 16,492 patients with Type 2 Diabetes Mellitus and a high-risk of cardiovascular events treated with current per oral antidiabetics and patients treated with saxagliptin or placebo. Eight thousand eight hundred and twenty patients were randomised to be treated with saxagliptin and 8,212 were randomised to be treated with placebo. The average monitored period was 2.1 years. RESULTS: The primary goal (cardiovascular death, nonfatal myocardial infarction and nonfatal CMP) occurred in 7.3% (613) patients treated with saxagliptin and in 7.2% (609) patients treated with placebo (HR 1.00, p < 0.001 for non inferiority). The main secondary goal (cardiovascular death, myocardial infarction, vascular stroke, hospitalisation for a heart failure or angina pectoris and myocardial revascularisation) occurred in 12.8% (1,059) patients treated with saxagliptin and in 12.4% (1,034) patients treated with placebo. The number of hospitalisations for heart failure was 289 (3.5%) in the group treated with saxagliptin and 228 (2.8%) in the group treated with placebo (p = 0.007). CONCLUSION: DPP 4 inhibitor saxagliptin did not increase the occurrence of ischemic cardiovascular events but it inclined to an increased hospitalisation for heart failure in patients with the already present heart failure. It did not increase the occurrence of pancreatitis. Simultaneously it significantly improved the Diabetes Mellitus control, which could signal a future improvement in cardiovascular goals.

Effect of low calorie diet and controlled fasting on insulin sensitivity and glucose metabolism in obese patients with type 1 diabetes mellitus.

Obesity in T1DM patients is associated with the components of metabolic syndrome. The influence of controlled fasting and low calorie diet (LCD) on insulin sensitivity and glucose metabolism was studied in 14 obese patients with type 1 diabetes mellitus (T1DM) (42.6+/-9.4 years, BMI 32.4+/-2.1 kg m(-2)). Insulin sensitivity in obese T1DM patients was measured using a hyperinsulinemic-euglycemic clamp before fasting, immediately after 7 days of fasting, and after 21 days of LCD. Glucose oxidation and non-oxidative glucose disposal were measured before and during the clamp by indirect calorimetry. In the control group of 13 of non-obese T1DM patients (36.9+/-13.9 years, BMI 22.6+/-2.1 kg m(-2)), only one hyperinsulinemic-euglycemic clamp was performed. Obese T1DM patients lost 6.1+/-1.1 kg after fasting and maintained reduction in body weight after 21 days of LCD. Fasting transiently reduced insulin-mediated glucose disposal in the clamp (from 9.69+/-1.48 to 6.78+/-1.21 mg min(-1) kg(-1), P<0.001). This was caused by reduced glucose oxidation after the fasting period (from 2.81+/-0.52 to 0.88+/-0.98 mg min(-1) kg(-1), P<0.001). We conclude that one week of fasting transiently decreased insulin-mediated glucose disposal in T1DM patients. This was caused by reduced glucose oxidation.

[An overview of so far published analyses comparating the effectiveness of the treatment with insulin pump and multiple daily injections in type 1 diabetes mellitus]. / Prehled dosud publikovaných analýz srovnávajících efektivitu lécby inzulinovou pumpou a rezimu nekolika injekcí inzulinu denne u diabetiku 1. typu.

The paper brings an overview of published systematic reviews and meta-analyses concerning the evaluation of the effectiveness of the treatment with insulin pump (CSII) in comparison with multiple daily injections (MDI) in type 1 diabetes mellitus. According to found works CSII leads to slightly lower levels of glycosylated hemoglobin (HbA1c) in patients with type 1 diabetes mellitus against MDI. The levels of HbA1c and the variability of glycaemia during the day on MDI before an initiation of CSII should serve for the prediction of an effect of CSII in particular patient. Type 1 diabetics on CSII have less often hypoglycaemia, higher flexibility of their daily regime and thus higher satisfaction with their treatment against MDI. The daily doses of insulin decrease. The weight of patients is the same or slightly higher after the initiation of CSII. There were not enough information for the assesment of the frequency of adverse reactions. It is necessary to educate each patient not only how to manipulate the particular insulin pump, but also about general recommendations for the treatment of diabetes and the application of insulin.

[An outlook to the future of pharmacotherapy for type 2 diabetes mellitus]. / Nahlédnutí do budoutnosti farmakoterapie diabetes mellitus 2. typu.

A new class of drugs that affect incretin system has been introduced in clinical practice, and renal glucose reabsorption inhibitors are soon to follow. Clinical practice thus has an access to drugs with mechanisms of action that differ from those of the currently available antidiabetics, and extend our ability to influence the multifaceted metabolic disorder associated with the type 2 diabetes. Nonpeptide molecules affecting GLP1 receptor and insulin mimetics are being tested in clinical trials. Research also continues in metabolic modulators of nuclear receptors, glucagon receptor antagonists and cellular glucocorticoid inhibitors. Promising are the compounds that increase glucose utilization (glucokinase activators) and decrease its release (fructose-1,6-diphosphatase inhibitors). Gene therapy is also likely to be used for the treatment of type 2 diabetes and its complications.

[Diabetes mellitus and the oral cavity]. / Diabetes mellitus a dutina ustní.

The paper summarizes current knowledge on the diseases of the oral cavity that may be related to diabetes mellitus. It draws the attention to the symptoms that signify potential association between the oral cavity disease and so far undiagnosed diabetes. Attention is paid to a connection between type 2 diabetes and periodontitis, as it is known that diabetes mellitus may contribute to the development of periodontitis, although a reciprocal link also exists and decompensated diabetes may be improved when periodontitis is cured.

[Motility disorders and gastric emptying in diabetes mellitus. Current diagnostics and treatment]. / Poruchy motility a evakuace zaludku u diabetika. Soucasné moznosti diagnostiky a lécby.

Autonomic neuropathy of the gastrointestinal tract is a common complication of diabetes mellitus. However, it is seldom recognised properly as it is rarely considered. In some patients, it might be asymptomatic or hardly compensatable diabetes can be the only one sign. There are non-invasive diagnostic methods to assess gastric emptying rate (13C-octanoic acid breath test) or myoelectric activity of the stomach (electrogastrography). The principle treatment comprises optimal control of diabetes and use of prokinetics.

[Dyspeptic syndrome associated with antidiabetic therapy]. / Dyspeptický syndrom pri antidiabetické lécbe.

Dyspeptic syndrome is a common complication of treatment with antidiabetic drugs. This may be a trivial as well as a very serious complication. Nausea, vomiting, diarrhoea, abdominal pain, loss of appetite and taste disturbances are the most common symptoms of dyspeptic problems in patients treated with metformin. They rarely are a reason for treatment discontinuation. Dyspeptic syndrome is a common complication in patients treated with acarbose, this may be prevented by reduced intake of sucrose. Pneumatosis cystoides intestinalis is a rare complication in acarbose-treated patients. Antiobesity agent orlistat is frequently associated with dyspeptic symptoms, particularly if fat intake is not reduced. Treatment with drugs affecting the incretin system (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) is very rarely complicated by acute pancreatitis. Glucagon-like peptide-1 receptor agonists may cause dyspeptic symptoms (nausea, vomiting, diarrhoea) at the beginning of treatment. These complaints usually cease and the treatment usually does not need to be discontinued.

[Care for diabetic patients with vascular disease]. / Péce o diabetika s cévním onemocnením.

There is an association between vascular complications and diabetes compensation in ambulatory as well as inpatient care. Diagnostics of vascular complications in diabetic patients are linked to increased risk of contrast-induced nephropathy. Treatment of severe vascular complications usually requires hospitalization. Achieving and maintaining target glycaemia is essential. Compensation of hyperglycaemia must be sufficient and timely; the risk of hypoglycaemia must not be ignored. Target glycaemia values must be adjusted individually, insulin administration is usually preferred.

[Conservative treatment of diabetic microangiopathy and macroangiopathy]. / Konzervativní lécba diabetické mikroangiopatie a makroangiopatie.

Vascular complications represent the most frequent and the most serious complication of diabetes type 1 and type 2. High attention is paid to all manifestations of microangiopathy and macroangiopathy not only in studies of their pathogenesis, but also in numerous clinical reports revealing significant effect of conservative treatment in vascular diseases. It concerns namely microalbuminuria and proteinuria and also to the manifestations of diabetic nephropathy which are largely affected by antihypertensive and fibrate treatment as well as to diabetic retinopathy treatable by fibrates. In the treatment of diabetic microangiopathy a consistent attention must be paid to the treatment of hypertension and dyslipidemia, preferably using combinations of hypolipidemics. Already during selection of antidiabetics, possible vascular effects should be considered. Vascular wall and manifestations of vascular diseases can be positively influenced by so called insulin sensitizers, derivatives of sulphonylurea and metformin. In preparation there exist some other substances for the treatment of diabetic complications. Already now, every medical doctor should be able to select adequate treatment with antihypertensives, hypolipidemics and antidiabetics for the prevention or therapy of vascular diabetic complications.

[Insulin sensitizing drugs]. / Inzulin senzitizující léky.

Currently, insulin sensitizing drugs in the form of metformin as the basic drug are part of the treatment of practically any type II diabetic patient. At the beginning of the therapy, metformin is used; later, insulin sensitizers (PPAR-gamma stimulators) such as rosiglitazone and pioglitazone are often applied. Nowadays, extensive research into new pharmaceuticals is being conducted in the group of insulin sensitizers. So-called double sensitizers, panPPAR sensitizers or PPAR-delta sensitizers, are being developed. The most promising group is of the PPAR-gamma selective modulators.

[Nutrition for the diabetic patient with kidney disease]. / Výziva diabetika s onemocnením ledvin.

Malnutrition is a major problem in chronically ill patients. The combination of diabetes and renal insufficiency increases the risk of malnutrition, also due to dietary interventions associated with the two diseases. Resulting malnutrition intensifies inflammatory activity and further compromises nutrition intake. This results in a vicious circle which significantly reduces the quality of life of the affected patients and increases their mortality. Proper nutritional care for such patients is an integral part of their treatment.

[Metformin and kidneys]. / Metformin a ledviny.

Metformin is currently recommended as the first-line drug for type 2 diabetic patients once the disease has been diagnosed. In addition to antihyperglycaemic effect, it has other effects which have a positive effect on cardiovascular risk. The greatest risk of metformin treatment is lactate acidosis, but its incidence is very low if the contraindications are observed. In spite of the fact that not all contraindications are observed in practice, the incidence of lactate acidosis demonstrably provoked by metformin does not grow. In spite of ongoing discussion on the subject, contraindications still include all states involving the risk of lactacidosis including renal insufficiency.

[Pharmacological treatment of diabetic retinopathy]. / Farmakologická lécba diabetické retinopatie.

Diabetic retinopathy is the most serious diabetic complication. Modern pharmacotherapy offers a wide range of potential treatments (ACE inhibitors, sartans, hypolipidemic drugs, drugs influencing proteinkinase C and vascular endotelial growth factor etc.). Diabetic retinopathy was previously treated surgically but today pharmacotherapy is becoming increasingly important. Undoubtly basic strategy for preventing diabetic retinopathy is antihyperglycemic therapy and normoglycemia.

Relation of cholesterol metabolism and non-cholesterol sterols to insulin resistance.

Using non-cholesterol sterols investigation several authors postulated a hypothesis that in the metabolic syndrome cholesterol endogenous synthesis is increased and its absorption decreased. Our study is the first attempt to evaluate the direct relation of cholesterol metabolism to the principal pathogenetic phenomenon of the metabolic syndrome--namely to insulin resistance. We have measured insulin sensitivity by two methods--Quicki (Quantitative Sensitivity Check Index) and intravenous insulin tolerance test (Kitt) and 3 indirect markers--fasting insulin level, fasting C-peptide level and SHBG (sex hormone binding globulin). The investigation was performed in three groups of subjects with a different prevalence of insulin resistance: 72 non-diabetics with ischemic heart disease, 117 young blood donors and 63 type 2 diabetics on diet therapy only. Analyzing altogether 60 relationships--between four sterols (lathosterol, squalene, sitosterol and campesterol) and five markers of insulin resistance in three groups of subjects--we have found only six significant relations between cholesterol synthesis and absorption and insulin resistance in all groups of patients. Our results indicate that there exists a significant relationship between insulin sensitivity and indices of either increased cholesterol synthesis or decreased cholesterol absorption. Insulin resistance explains only a part of both abnormalities mentioned above.

[Sodium hyaluronate and an iodine complex--Hyiodine--new method of diabetic defects treatment]. / Komplex hyaluronanu a jódu--hyiodine--nova metoda pri terapii diabetických defektu.

UNLABELLED: Complicated diabetic defects are difficult to heal and frequently result in leg amputation. We have developed a new and unique system for wound treatment, which is based on combination of high molecular weight sodium hyaluronate with an iodine complex--Hyiodine. The aim of our study was to assess the effect of this new method of wound dressing on infected diabetic defects healing. METHODS: The effect of Hyiodine was studied on 22 patients suffering from complicated foot diabetic wounds. Hyiodine was either spread directly over the wound, or (more frequently) gauze was immersed in Hyiodine and then put on/into the wound. Then several layers of dry gauze covered the wound. RESULTS: Within 2-6 weeks after the onset of treatment all but two defects were filled with granulation tissue. Complete healing was evident in 18 patients within 6-20 weeks after the start of treatment, depending on the wound character, localization and extent. Two patients are still treated by Hyiodine, and significant improvement is apparent on their wound. Treatment was not successful in two subjects with ischemic defects due to simultaneous arterial occlusion. CONCLUSIONS: We can conclude that the hyaluronan-iodine complex Hyiodine is efficient method for treatment of difficult to heal diabetic defects without complete arterial occlusion.

[A role of diabetologist in management of infections in diabetics]. / Uloha diabetologa pri infekcním onemocnení diabetika.

The important role of diabetologists in management of infections in diabetics is the quality diabetes control and compensation. There are two main arrangements in the management, the correction of the former antidiabetic therapy and the quality nutrition. The insulin resistance is higher by any infection and the insulin requirement is higher in such conditions. It is necessary to stop the metformin therapy, provide basal insulinemia and level up the insulin dose at least by one third. In the heavy infections the continuous intravenous insulin infusion is recommend. The specialities of the infection in diabetics, the prevention of infection and acute diabetes complications are discussed.

[Clinical importance of Helicobacter pylori infection in patients with diabetes mellitus]. / Klinický význam infekce Helicobacter pylori u nemocných s diabetes mellitus.

This paper provides a review of current literature on Helicobacter pylori infection in diabetes mellitus. According to majority of studies there is no difference of Helicobacter pylori infection prevalence between diabetes mellitus and general population. There is no role of Helicobacter pylori in etiopathogenesis of diabetes. The only finding of Helicobacter pylori itself has not been an indication for eradication therapy in diabetes. In case of anti-helicobacter therapy (due to another indication) eradication rate is lower in diabetics (compared to non-diabetics) and there is a higher risk of re-infection (compared to general population). Several issues (especially dysmotility disorders of the stomach and influence of Helicobacter pylori eradication for the control of diabetes) remain controversial.