Manifestation Of Insulin Resistance Research Articles

Correction of insulin resistance in patients with chronic obstructive pulmonary disease under the influence of recovery treatment

According to modern concepts chronic obstructive pulmonary disease (COPD) is accompanied by persistent respiratory symptoms, as well as extrapulmonary systemic manifestations. Insulin resistance and metabolic syndrome belong to the leading causes of comorbidity formation. The aim is to study the possibilities of insulin resistance correction in COPD patients, taking into account the previous COVID-19, under the influence of complex non-pharmacological treatment based on haloaero­soltherapy in connection with the applied treatment complex. Clinical and functional examinations and carbohydrate metabolism investigations were carried out in 115 patients with COPD (GOLD II-III) beyond the acute period before and after the course of recovery treatment. Among them 60 patients were convalescents after COVID-19. The average age of patients was 60,3±1,71 years and duration of COPD – 14,2±0,89 years. 12 practically healthy persons were also exa­mined as a control group. The presence of insulin resistance was diagnosed by evaluation of the glucose, insulin, HOMA-IR index and C-peptide levels. Treatment was carried out according to three treatment complexes. The main component of the treatment was the use of haloaerosoltherapy and its combination with singlet oxygen therapy or drinking and inhalation of mineral water. The duration of the course of treatment was 20-21 days. Before treatment the presence of insulin resistance was confirmed in both groups of patients with COPD (without COVID-19 and convalescents after COVID-19). Blood glucose levels were significantly higher in the latter group. After the course of recovery treatment a decrease in insulin resistance was noted, especially in patients who received complex treatment, although complete normalization of the studied indices was not achieved. Thus, insulin resistance is a characteristic, pathogenetically determined metabolic manifestation in COPD, which requires constant monitoring and development of long-term programs of complex clinical management of this contingent of patients, especially beyond the exacerbation period. The use of haloaerosoltherapy, which has a sanative and anti-inflammatory effect and promotes clinical stabilization of COPD, is accompanied by a decrease in the manifestations of insulin resistance. Expressiveness of these changes depend on the applied treatment complex. The most pronounced decrease in insulin resistance in COPD patients was noted under the influence of complex treatment based on haloaerosoltherapy with additional drinking and inhalation use of low-mineralized hydrocarbonate siliceous mineral water.

Clinical Profile of Patients with Polycystic Ovary Syndrome at Tertiary Care Hospital

Polycystic ovary syndrome, with an incidence of up to 10%, is one of the communal causes of anovulation in females of reproductive age. Diagnostic criteria for PCOS include enlarged polycystic ovaries, obesity, hirsutism, and oligomenorrhea. These women are more susceptible to endometrial cancer, type II diabetes, dyslipidemia and premature atherosclerosis. Objective: The aim of this study was to determine the different clinical profiles of PCOS patients and to educate patients about the long-term outcomes related with this condition. Methods: This cross-sectional study was conducted at the obstetrics and gynaecology department of Ayub Teaching Hospital, Abbottabad for the duration from 1st January 2019 to 31st December 2019. The study included 110 people with oligomenorrhea, obesity, acne, infertility and hirsutism. Young women who had their menarche less than two years ago, women over 45 years of age, and patients receiving exogenous estrogen or progesterone therapy were excluded from the study. For the social sciences, data was entered and analyzed with SPSS 25.0. The percentages and mean values were determined for several parameters. Results: Of the 110 patients selected for this study, 46 (41.8%) were married and 64 (58.2%) were unmarried. In contrast to rural areas, there were more patients from urban areas (63.6% vs 36.4%). 6.4% of patients were underweight, 20% and 59.1% were overweight and obese. Most patients (71.8%) had oligomenorrhea or amenorrhea. 70% of patients gained weight, many of whom attributed this to menstrual problems. Infertility affected 30% of married patients. Hirsutism and acne were found in 21.8% and 25.5%, respectively. Acanthosis Nigricans, a manifestation of insulin resistance, was found in 31.8% of patients. Eight patients were taking medication for hyperprolactinemia, ten women (10%) had type 2 diabetes taking oral hypoglycemics for glycemic control, and six had hypertension. All patients underwent USG and 85 (77.3%) of them showed a characteristic necklace pattern of follicular arrangement. Conclusion: Using clinical features and ultrasonography in women, PCOS can be accurately diagnosed using the Rotterdam criteria. The two main findings we observed in our patients were weight gain and amenorrhea or oligomenorrhea. It is very important to inform and educate unmarried patients with PCOS about the relationship of this condition with infertility and chronic health problems. Keywords: Oligomenorrhea, PCOS, Anovulation and obesity

Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world and one of the leading indications for liver transplantation. It is one of the many manifestations of insulin resistance and metabolic syndrome as well as an independent risk factor for cardiovascular disease. There is growing evidence linking the incidence of NAFLD with psychiatric illnesses such as schizophrenia, bipolar disorder and depression mechanistically via genetic, metabolic, inflammatory and environmental factors including smoking and psychiatric medications. Indeed, patients prescribed antipsychotic medications, regardless of diagnosis, have higher incidence of NAFLD than population norms. The mechanistic pharmacology of antipsychotic-associated NAFLD is beginning to emerge. In this review, we aim to discuss the pathophysiology of NAFLD including its risk factors, insulin resistance and systemic inflammation as well as its intersection with psychiatric illnesses.

1421-P: Long-Term Type 2 Diabetes Remission after Bariatric Surgery in Patients with and without Liver Steatosis

Background: Nonalcoholic steatohepatitis (NASH) is considered the hepatic manifestation of insulin resistance. Therefore, we aimed to assess the association between biopsy-proven liver steatosis and long-term remission of type 2 diabetes (T2D) 8 years following different bariatric procedures. Methods: In a retrospective cohort study including 249 patients with and without T2D, the association between biopsy-proven NASH and long-term remission of T2D 8 years following sleeve gastrectomy (SG) and Roux-enY-gastric bypass (RYGB) has been assessed. Results: Out of 249 patients, 15.3% showed NASH and T2D at the time of surgery. 8 years after surgery, T2D remission was achieved in 44.7% of patients with NASH compared to 76.0% without NASH. Patients with T2D remission were younger, had higher BMI, displayed lower HbA1c and lower preoperative insulin use (p<0.001) . Patients without remission of T2D showed higher steatosis scores (p<0.05) . In a multivariate logistic regression, higher preoperative HbA1c (OR 0.41) , insulin use (OR 0.16) and preexisting liver fibrosis (OR 0.19) decreased the probability of long-term T2D remission (p<0.05) . Liver steatosis, hepatocyte ballooning or lobular inflammation were not significantly associated with T2D remission. Patients without T2D were predominantly female, of younger age (p<0.001) and displayed lower scores of steatosis, hepatocyte ballooning and lobular inflammation (p<0.05) . With regard to type of surgery, there was no significant difference in T2D remission. Discussion and Conclusion: Our data suggest that long-term remission of T2D after bariatric surgery (BS) is associated with lower preoperative insulin use and lower biopsy-proven steatosis scores in patients with NASH. Furthermore, T2D remission might be less likely in patients with liver fibrosis. Type of surgery did not affect T2D remission. Our results might help identify patients with NAFLD who benefit most from BS with regard to glycemic outcomes long-term. Disclosure A.Lautenbach: Advisory Panel; Novo Nordisk, Speaker's Bureau; Boehringer Ingelheim International GmbH, Novo Nordisk. M.Wernecke: None. S.M.Meyhöfer: None. S.Meyhöfer: None. F.D.Stoll: None. J.Aberel: Advisory Panel; Novo Nordisk, Speaker's Bureau; Novo Nordisk.

Особливості вуглеводного обміну у жінок раннього репродуктивного віку із склерополікістозом яєчників

Актуальність. Фертильність жінок, особливо з ендокринним гіперандрогенним дисбалансом, заслуговує на особливу увагу, оскільки частота репродуктивних втрат у цій групі сягає майже 67 %. Мета. Визначення взаємозв’язку між індексом маси тіла, порушеннями вуглеводного обміну та показником вітаміну D при клінічних симптомах склерополікістозу яєчників (СПКЯ). Матеріали та методи. Гормональний аналіз проведено упродовж п’ятого — сьомого днів менструального циклу на підставі визначення у сироватці крові фолікулостимулюючого, лютеїнізуючого гормонів, тестостерону, глобуліну, що зв’язує статеві гормони, дегідроепіандростерону сульфату, дегідротестостерону у 45 жінок із СПКЯ віком 18–25 років. Результати. Прослідковано зв’язки вмісту вітаміну D і гормонального забезпечення репродуктивної системи у жінок із СПКЯ, продемонстровано тригерну роль зниження рівня вітаміну D у формуванні гормонального дисбалансу та клінічних гіперандрогенних проявів інсулінорезистентності у жінок із СПКЯ. Висновки. Па­цієнтки із СПКЯ та недостатнім рівнем вітаміну D, незважаючи на відсутність надмірної маси тіла та ожиріння, мають більш виражені зміни вуглеводного обміну, ніж пацієнтки без СПКЯ.

The Importance of Insulin Resistance Assessing as the Effectiveness Predictor in Rehabilitation and Observation of Patients after Acute Myocardial Infarction

One of the goals for the management of patients after acute myocardial infarction is to achieve and maintain the optimal level of lowdensitylipoproteins (LDL), which is a factor that determines the prognosis in patients with coronary heart disease. A relevant objectiveis to extract from a number of trophic indicators that indicate disturbance in the adipose tissue distribution and functioning and thatincrease the risk of repeated cardiovascular disasters, the predictors of the low-density lipoprotein targets achieving effectivenessduring rehabilitation and subsequent dispensary follow-up of patients who have suffered a myocardial infarction. Aim. To assess the role of trophological factors, in particular insulin resistance, in achieving LDL cholesterol target values during rehabilitationand follow-up of patients after acute myocardial infarction. Material and methods. The study included 68 men (age from 55 to 65 years) after myocardial infarction underwent rehabilitation atthe Ivanovo State Medical Academy Clinic. The dynamics of the lipidogram parameters over the course of 6 months was evaluated. Todescribe the trophological status of the patients several metabolic and anthropometrical indicators were applied (weight, body massindex, waist circumference, ratio of waist circumference to the hips circumference, index of the central obesity, visceral adiposity index,percentage of fatty tissue, and metabolic index of insulin resistance). A regression model was created to determine significant factorsassociated with achieving low-density lipoprotein cholesterol targets values. Results. The effectiveness of dyslipidemia correction in patients with myocardial infarction was lower in the group of people with signsof insulin resistance. Among the trophic indicators, predictors that have a prognostic value in achieving the target level of low-densitylipoprotein cholesterol are identified: the initial level of low-density lipoprotein cholesterol, the central obesity index, the metabolicinitial index and after 6 months of follow-up. Conclusion. In the course of rehabilitation and subsequent follow-up, it is advisable to distinguish among patients after acute myocardialinfarction, persons with a metabolically unhealthy phenotype and insulin resistance. If an increase in the metabolic central obesityindex is recorded, it is possible to regard the manifestations of insulin resistance as a predictor of the ineffectiveness of achieving thegoals of lipid-lowering therapy and adjust therapeutic and preventive measures.

The use of inositol stereoisomers for the treatment of patients with clinical and biochemical signs of hyperandrogenism

For many years, the use of combined oral contraceptives (COC) with antiandrogenic effects was the main treatment of clinical and biochemical hyperandrogenism in patients with polycystic ovary syndrome (PCOS). At the same time, the creation of an alternative therapy regimen for patients who have contraindications to taking hormonal drugs, as well as planning pregnancy, is obvious. Various combinations of inositol stereoisomers (myoinositol ― MI, and D-chiro-inositol ― DCI) are being actively studied. The review reflects the current understanding of the etiology, pathogenesis of hyperinsulinemia and androgen-dependent dermatological manifestations of polycystic ovary syndrome. The mechanisms of action of inositols at the molecular level are normalization of carbohydrate metabolism in the body and the reduction of hyperinsulinemia, as well as the levels of male sex hormones in PCOS. A comparative analysis of studies with various combinations of inositols was conducted on the effectiveness of treatment of clinical manifestations of hyperandrogenism, such as hirsutism and acne. The use of MI in conjunction with DCI reduces the risk of developing metabolic syndrome and improves the endocrine profile and manifestations of insulin resistance, but further multicenter studies on this problem are required.

Plasma paraoxonase1 activity in rats treated with monocrotophos: a study of the effect of duration of exposure.

We have earlier demonstrated the potential of monocrotophos (MCP), a highly toxic organophosphorus insecticide (OPI), to elicit insulin resistance in rats after chronic exposure. Given the understanding of role of paraoxonase1 (PON1) in OPI toxicity and diabetes pathology, this study was envisaged to understand the effect of duration of exposure to MCP on plasma PON1 activity in rats. Rats were administered MCP per os at 1/20 and 1/10th LD50 as daily doses for 180 days. Interim blood samples were collected at 15, 30, 45, 90 and 180 d for analysis of plasma parameters. Exposure to MCP for 45 resulted in persistent trend of hyperinsulinemia, while significant increase in fasting glucose levels was observed after 180 days. MCP caused suppression of plasma cholinesterase activity though the study period, albeit extent of inhibition was more severe during the early phase of the study. Exposure to MCP for 180 d resulted in hypertriglyceridemia and marginal decrease in HDL-C levels. MCP failed to modulate PON1 activity in plasma during the early phase of the study (up to 45 d). However, prolonged exposure resulted in significant increase in the plasma PON1 activity. This suggests that manifestation of insulin resistance in rats subjected to chronic exposure to MCP is associated with increase in PON1 activity. Our work provides rationale for studying whether the increase in PON1 activity observed in the present study serves to counter the deleterious effect of long term exposure to organophosphorus insecticides on metabolic homeostasis.

Prevention of Type 2 Diabetes: A Cardiologist's Perspective

Based on the results of numerous clinical trials, it has been proved that type 2 diabetes is one of the main risk factors for the development of cardiovascular diseases and cardiovascular mortality. The article reviews the features of the development of cardiovascular pathology in patients with carbohydrate metabolism disorders and diabetes. Chronic hyperglycemia is not only the main manifestation of the disease, but also an important pathogenetic factor in the development of almost all of its complications - micro-, macroangiopathies and neuropathies. The prevalence of arterial hypertension among patients with diabetes mellitus is noteworthy, the frequency of which is almost twice as high as in people without diabetes. In the presence of diabetes mellitus, such risk factors for cardiovascular complications as obesity, dyslipidemia, microalbuminuria are manifested, the risk of development of macrovascular (myocardial infarction, stroke) and microvascular (nephropathy, retinopathy, etc.) complications is significantly increased.In accordance with the recommendations of the European Society of Cardiology and the European Society of Atherosclerosis (EOA / EOA) for the treatment of dyslipidemia (2016), patients with type 2 diabetes mellitus are automatically classified as high or very high cardiovascular risk and are equated to patients with confirmed atherosclerotic cardiovascular disease (coronary heart disease, stroke, transient ischemic attack, peripheral arterial disease). In accordance with these recommendations, patients with diabetes mellitus and high cardiovascular risk should be given a high-intensity statin therapy for the purpose of secondary or primary prevention of cardiovascular diseases.The results of a number of studies have shown that already at the stage of early disorders of carbohydrate metabolism (prediabetes) there are manifestations of insulin resistance, compensatory hyperinsulinemia and there is an accumulation of risk factors that contribute to the launch of the pathophysiological cascade of atherosclerosis of coronary, cerebral and peripheral vessels. Thus, prediabetes is not only an intermediate stage in the development of type 2 diabetes mellitus, but also an independent risk factor for cardiovascular diseases. Quite often, type 2 diabetes mellitus debuts directly as vascular complications - myocardial infarction, cerebral stroke. Therefore, it is recommended to identify patients with a high risk of type 2 diabetes as early as possible and actively perform the correction of hyperglycemia, dyslipidemia, arterial hypertension and other risk factors for cardiovascular diseases.

Hypertriglyceridemia per se Is Not an Independent Risk Factor for Beta-Cell Dysfunction

Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta-cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects. To circumvent this limitation, we took advantage of apolipoprotein C3 (ApoC3)-transgenic mice, a model with genetic predisposition to hypertriglyceridemia without alterations in glucose metabolism. We showed that ApoC3-transgenic mice, as opposed to age/sex matched wild type littermates, develop hypertriglyceridemia with concomitant elevations in plasma cholesterol and non-esterified fatty acid levels. Anti-insulin and anti-glucagon dual immunohistochemistry in combination with morphometric analysis revealed that ApoC3-transgenic and wild type littermates had similar beta-cell and alpha-cell masses as well as islet size and architecture. These effects correlated with similar amplitudes of glucose-stimulated insulin secretion and similar degrees of postprandial glucose excursion in ApoC3-transgenic vs. wild type littermates. ApoC3-transgenic mice did not visualize lipid infiltration into islets, correlating with the lack of ectopic triglyceride and cholesterol depositions in the pancreata. ApoC3-transgenic mice, despite persistent hypertriglyceridemia, maintained euglycemia under both fed and fasting conditions without manifestation of insulin resistance and fasting hyperinsulinemia. We concluded that hypertriglyceridemia per se is not an independent risk factor for beta-cell dysfunction. Disclosure J. Yamauchi: None. T. Zhang: None. S. Lee: None. H. Dong: None.

INFLUENCE OF DIFFERENT CLASSES OF ANTIHYPERTENSIVE DRUGS ON INSULIN RESISTANCE IN PATIENTS WITH MILD AND MODERATE ARTERIAL HYPERTENSION

Objective: To reveal the prevalence of metabolic syndrome in patients with hypertension and methods of correction with antihypertensive therapy. Design and method: 223 patients with mild to moderate hypertension (AH) and metabolic syndrome (MS) were screened according to ATP III criteria, of which 105 (47.1%) were males and 118 (52.9%) were females. The average age of patients was 50.29 ± 0.96 years. The average duration of hypertension is 5.01 ± 0.26 years. The average for the office of SBP and DBP was to 157.03 ± 0.79 and 92.17 ± 0.32 mm Hg., heart rate - 75.02 ± 0.69 beats/min. Average daily blood pressure monitoring were 135.90 ± 1.13/80.38 ± 0.81 mm Hg. Patients was devided for groups takes for 6 months atenolol, nebivolol, carvedilol, bisoprolol, fosinopril, telmisartan. Results: Assessing the effect of drugs on the state of insulin resistance, it was found that atenolol, in contrast to fosinopril and telmisartan, significantly impaired IR, which was manifested in an increase in HOMA level by 78.18%, p < 0.05. At the same time, against the background of treatment with fosinopril the HOMA index decreased by 12.5%. However, an even more pronounced improvement in IR was observed in the treatment of telmisartan, HOMA decreased by 31.64%, p < 0.05. The difference between the telmisartan and fosinopril group is significant, p < 0.05. Therapy with carvedilol contributed to a significant decrease in HOMA by 21.7%, p < 0.05. On the background of treatment with bisoprolol, HOMA decreased by 17.4%, p < 0.05, in the group of nebivolol HOMA decreased by 23%, p < 0.05. Thus, telmisartan and nebivolol had the highest positive effect on IR. Conclusions: The use of telmisartan and nebivolol as monotherapy can be rational in patients with mild to moderate arterial hypertension and the clinical signs of a metabolic syndrome without diabetes with manifestations of insulin resistance.

AT1 Receptor Blockade Improves Mitochondrial Activity in Insulin Resistant but not Type II Diabetic Hearts

Hyperglycemia increases the risk of oxidant overproduction in the heart through activation of a multitude of pathways. Oxidation of mitochondrial enzymes may impair their function resulting in accumulation of intermediates and reverse electron transfer, contributing to mitochondrial dysfunction. Furthermore, the renin‐angiotensin system (RAS) becomes inappropriately activated during metabolic syndrome, increasing oxidant production through NAPDH assemblage. To test the acute effects of an oral glucose tolerance test (oGTT) on the insulin resistant and type II diabetic hearts, 16 and 25 week old animals were given a glucose tolerance test prior to dissection. Adult male rats were randomly assigned to three groups prior to dissection (n= 5–8 animals/group/time point): 1) Long Evans Tokushima Otsuka (LETO; lean strain‐control), 2) insulin resistant, obese Otsuka Long Evans Tokushima Fatty (OLETF), and 3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d x 6–8 weeks). Hearts were collected at T0, T60, and T120 minutes post‐glucose infusion and at T0, T180, and T360 in 25‐week‐old animals. Aconitase activity was not changed between LETO and OLETF rats at T0, but was increased five‐fold with ARB treatment. At T60 aconitase activity was decreased 69% in OLETF from LETO, but ARB treatment increased activity six‐fold. AT 25 weeks of age aconitase activity was two‐fold higher in OLETF compared to LETO and remained unchanged through T360. ARB treatment lowered this activity to LETO levels at T0 only. Complex I activity had no detectable difference between LETO and OLETF in 16 week old animals; however, ARB increased activity by 50%. However, in 25 week old animals complex I was lowered 32% from LETO and ARB treatment had no effect on complex I activity. At T60, complex II activity was decreased 30% from LETO in OLETF rats, and ARB treatment increased complex II activity by 79%. In 25 week old animals OLETF rats had increased complex II activity at T180 by 34%, which then was restored to baseline by T360. ARB treatment increased activity by 26%, but maintained this increase over the 6 hour span. These data demonstrate the protective effects of AT1 blockade on cardiac mitochondrial function during the manifestation of insulin resistance, but demonstrate that its protective effects diminish as animals transition into a frank diabetic stage.Support or Funding InformationM. Thorwald and R. Rodriguez were supported by NIH NCMHD9T37MD001480. R.M. Ortiz was partially supported by NIH NHLBIK02HL103787. Research was partially funded by NIH NHLBIR01HL091767.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A dramatic improvement in metabolic parameters and cutaneous manifestations of insulin-resistance in a type 2 diabetic patient with Congenital Generalized Lipodystrophy (Berardinelli-Seip Syndrome) treated with pioglitazone

A dramatic improvement in metabolic parameters and cutaneous manifestations of insulin-resistance in a type 2 diabetic patient with Congenital Generalized Lipodystrophy (Berardinelli-Seip Syndrome) treated with pioglitazone

Nephrolithiasis

Nephrolithiasis is a highly prevalent condition, but its incidence varies depending on race, gender, and geographic location. Approximately half of patients form at least one recurrent stone within 10 years of the first episode. Renal stones are usually composed of calcium salts (calcium oxalate monohydrate or dihydrate, calcium phosphate), uric acid, or, less frequently, cystine and struvite (magnesium, ammonium, and phosphate). Calcium oxalate stones, the most commonly encountered ones, may result from urinary calcium oxalate precipitation on the Randall plaque, which is a hydroxyapatite deposit in the interstitium of the kidney medulla. Uric acid nephrolithiasis, which is common among patients with metabolic syndrome or diabetes mellitus, is caused by an excessively acidic urinary pH as a renal manifestation of insulin resistance. The medical evaluation of the kidney stone patient must be focused on identifying anatomic abnormalities of the urinary tract, associated systemic diseases, use of lithogenic drugs or supplements, and, mostly, urinary risk factors such as low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH that can be affected by dietary habits, environmental factors, and genetic traits. Metabolic evaluation requires a urinalysis, stone analysis (if available), serum chemistry, and urinary parameters, preferably obtained by two nonconsecutive 24-hour urine collections under a random diet. Targeted medication and dietary advice are effective to reduce the risk of recurrence. Clinical, radiologic, and laboratory follow-ups are needed to prevent stone growth and new stone formation, to assess treatment adherence or effectiveness to dietary recommendations, and to allow adjustment of pharmacologic treatment. This review contains 5 highly rendered figure, 3 tables, and 105 references.

The mechanisms underlying the therapeutic effects of reflexotherapy and drinking mineral waters in the patients presenting with metabolic syndrome

The objective of the present study was to evaluate the effects produced by the intake of drinking mineral water and acupuncture on the various parameters characterizing the patients suffering from metabolic syndrome in combination with altered insulin resistance. Ninety patients with this condition included in the study underwent the analysis of their the blood pressure, body mass index, blood glucose and lipid levels, insulin and cortisol secretion. We undertook the analysis of the effects of the single and repeated intakes of Essentuki No 17 mineral water included in the combined treatment of the patients with metabolic syndrome and revealed many common responses of the organism to its therapeutic action. Specifically, the stress-type reactions suggested the initiation of the adaptive processes in the system of hormonal regulation of carbohydrate and lipid metabolism. Simultaneously, the manifestations of insulin resistance became less pronounced indicating that both acupuncture and drinking mineral water suppressed the action of the main pathogenic mechanisms underlying the development of metabolic syndrome. Moreover, it was shown that acupuncture had a stronger hypotensive effect in the combination with the decrease of the overproduction of cortisol whereas the intake of the mineral water had a greater metabolic potential and contributed to the intensification of the basal secretion of glucocorticoids. Both reflexotherapy and drinking mineral water have a well apparent effect on the pathogenetic reactions of the metabolic syndrome and therefore can be used in addition to the standard therapy to activate the non-specific, phylogenetically established and enshrined at the genetic level self-healing responses by mainstreaming the adaptation processes and the formation of the adaptive reactions initiated by stressor components. The addition of acupuncture or domestic mineral water intake to the standard therapy of the patients suffering from metabolic syndrome significantly enhances the effectiveness of the treatment. The beneficial therapeutic action of acupuncture and drinking mineral water is underlain by their impact on the mechanisms of resistance to insulin that manifests itself as a decrease of the fasting secretion of this hormone and optimization of carbohydrate and lipid metabolism. The therapeutic effect of acupuncture and drinking mineral water is realized through the induction of the stress-initiating reactions which activate the processes of adaptation, with reflexotherapy largely acting on the cardiovascular system and drinking mineral water on the system responsible for insulin regulation of the metabolic processes.

Effect of Hypertriglyceridemia on Beta Cell Mass and Function in ApoC3 Transgenic Mice

Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects. To circumvent this limitation, we took advantage of apolipoprotein C3 (ApoC3)-transgenic mice, a model with genetic predisposition to hypertriglyceridemia. We showed that ApoC3-transgenic mice, as opposed to age/sex-matched wild-type littermates, develop hypertriglyceridemia with concomitant elevations in plasma cholesterol and non-esterified fatty acid levels. Anti-insulin and anti-glucagon dual immunohistochemistry in combination with morphometric analysis revealed that ApoC3-transgenic and wild-type littermates had similar beta cell and alpha cell masses as well as islet size and architecture. These effects correlated with similar amplitudes of glucose-stimulated insulin secretion and similar degrees of postprandial glucose excursion in ApoC3-transgenic versus wild-type littermates. Oil Red O histology did not visualize lipid infiltration into islets, correlating with the lack of ectopic triglyceride and cholesterol depositions in the pancreata of ApoC3-transgenic versus wild-type littermates. ApoC3-transgenic mice, despite persistent hypertriglyceridemia, maintained euglycemia under both fed and fasting conditions without manifestation of insulin resistance and fasting hyperinsulinemia. Thus, hypertriglyceridemia per se is not an independent risk factor for beta cell dysfunction in ApoC3 transgenic mice.

BIOCHEMICAL MARKERS OF VASCULAR DISFUNCTION INDUCED BY TYPE 2 DIABETES IN FEMALE RATS WITH NORMO- OR HYPOESTROGENIC STATE

The effect of estrogen deficiency on the biochemical parameters of vascular dysfunction induced by type 2 diabetes in female rats was investigated. It was shown that hypoestrogenic state in combination with diabetes promotes more expressive manifestation of insulin resistance and enhances oxidative stress in the blood serum. However, estrogens level does not influence on the hyperglycemia development and changes in activity of nitric oxide synthase and heme oxygenase in the vessels of diabetic animals.

Prolactin (PRL) in adipose tissue: regulation and functions.

New information concerning the effects of prolactin (PRL) on metabolic processes warrants reevaluation of its overall metabolic actions. PRL affects metabolic homeostasis by regulating key enzymes and transporters associated with glucose and lipid metabolism in several target organs. In the lactating mammary gland, PRL increases the production of milk proteins, lactose, and lipids. In adipose tissue, PRL generally suppresses lipid storage and adipokine release and affect adipogenesis. A specific case is made for PRL in the human breast and adipose tissues, where it acts as a circulating hormone and an autocrine/paracrine factor. Although its overall effects on body composition are both modest and species-specific, PRL may be involved in the manifestation of insulin resistance.

Editorial: Exploring Lipid-related Treatment Options for the Treatment of NASH

The liver plays a major role in lipid metabolism, importing free fatty acids (FFA) and manufacturing, storing and exporting lipids: derangements in any of these processes can lead to non-alcoholic fatty liver disease (NAFLD) [1]. NAFLD can be seen as the result of an imbalance between lipid availability and lipid disposal resulting in hepatic steatosis [2]. NAFLD is considered by many as the hepatic manifestation of insulin resistance (IR) and is strongly associated with the metabolic syndrome [3]. The rapid increase in obesity and diabetes mellitus (DM) during the last decade is associated with an increase in the prevalence of NAFLD, making it the most common cause of chronic liver disease in the Western countries with up to 30% of the population affected [4]. Histological evaluation is the gold standard for precisely estimating the degree of liver damage caused by simple steatosis or by non-alcoholic steatohepatitis (NASH).

Effects of high-fat diet and the anti-diabetic drug metformin on circulating GLP-1 and the relative number of intestinal L-cells.

BackgroundElevated serum free fatty acids (FFAs) contribute to the pathogenesis of type-2-diabetes (T2D), and lipotoxicity is observed in many cell types. We recently showed that simulated hyperlipidemia induces lipoapoptosis also in GLP-1-secreting L-cells in vitro, while metformin confers lipoprotection.The aim of this study was to determine if a high fat diet (HFD) reduces the number of enteroendocrine L-cells and/or GLP-1 plasma levels in a rodent model, and potential effects thereupon of metformin treatment.MethodsC57/Bl6 mice received control/HFD for 12-weeks, and oral administration of metformin/saline for the last 14 days. Blood glucose, glycosylated hemoglobin and plasma insulin and GLP-1 were determined before and after treatment with metformin using ELISAs. GLP-1-immunopositive cells in intestinal tissue sections were quantified using immunohistochemistry.ResultsA HFD increased blood glucose, glycosylated hemoglobin, and fasting plasma insulin (33%, 15% and 70% increase, respectively), in conjunction with reduced oral glucose tolerance, indicating the manifestation of insulin resistance. Metformin counteracted these adverse effects, while also reducing prandial plasma FFAs. The number of GLP-1-positive cells was indicated to be reduced (55% reduction of the number of GLP-1-positive cells, p = 0.134), while there was a trend toward increased prandial plasma GLP-1 despite reduced food intake following a HFD.ConclusionHFD-fed mice rapidly develop insulin resistance. Metformin exerts beneficial glucose lowering effects, and is indicated to improve the incretin response. Albeit no significant effect, a HFD tends to reduce the number of GLP-1-positive cells. However, considering concurrent normal or increased plasma GLP-1, any reduction in the number of GLP-1-positive cells, probably does not contribute to development of the glucose intolerance, but may contribute to progression of the diabetic state through eventual loss of a functional incretin response.