Insulin Resistance In Men Research Articles

Sex hormone binding globulin (SHBG) serum levels and insulin resistance in men on chronic hemodialysis

BackgroundIn males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance.MethodsIn a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose.Results27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other.ConclusionsOur findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.

Peculiarity of Insulin Resistance in Men with Type 2 Diabetes Mellitus and Overall, Gender Comparison of Associated Complications

Peculiarity of Insulin Resistance in Men with Type 2 Diabetes Mellitus and Overall, Gender Comparison of Associated Complications

Testosterone therapy reduces insulin resistance in men with adult-onset testosterone deficiency and metabolic syndrome. Results from the Moscow Study, a randomized controlled trial with an open-label phase.

To describe changes in homeostasis model assessment of insulin resistance index (HOMA-IR) following testosterone therapy in men with hypogonadism and metabolic syndrome (MetS). A randomized, placebo-controlled, double-blind randomized controlled trial (RCT) comprising 184 men with MetS and hypogonadism (testosterone undecanoate [TU]: 113 men, placebo: 71 men) was conducted. This was followed by an open-label phase in which all men were given TU. We focused on men who were not receiving antiglycaemic agents (TU: 81 men; placebo: 54 men) as these could affect HOMA-IR. Inter-group comparison of HOMA-IR was restricted to the RCT (30 weeks), whilst intra-group comparison was carried out on men provided TU during the RCT and open-label phases (study cohort) and men given placebo during the RCT and then switched to TU during the open-label phase (confirmatory cohort). Regression analysis was performed to identify factors associated with change in HOMA-IR (∆HOMA-IR). The median HOMA-IR was significantly reduced at almost every time point (after 18 weeks) compared to baseline in men receiving TU in both the study and confirmatory cohorts. There was a significant decrease in median values of fasting glucose (30 weeks: -2.1%; 138 weeks: -4.9%) and insulin (30 weeks: -10.5%; 138 weeks: -35.5%) after TU treatment. Placebo was not associated with significant ∆HOMA-IR. The only consistent predictor of HOMA-IR decrease following TU treatment was baseline HOMA-IR (r2 ≥ 0.64). Baseline HOMA-IR predicted ΔHOMA-IR, with a greater percentage change in insulin than in fasting glucose. In men with MetS/type 2 diabetes (T2DM) not on antiglycaemic therapy, improvements in HOMA-IR may be greater than suggested by change in fasting glucose. Our results suggest that hypogonadism screening be included in the management of men with MetS/T2DM.

Calcium-phosphate homeostasis and insulin resistance in men

Background and aimsData on P homeostasis in insulin resistance (IR) are still conflicting. We investigated calcium-phosphate homeostasis parameters in men with/without IR. Methods and results177 volunteers (aged 61.62 ± 12.11), whose body mass index (BMI) was 29.97 ± 6.35, were studied. On fasting blood and spot urine samples, we measured serum creatinine, sodium (sNa), potassium (sK), chloride (sCl), calcium (sCa), phosphate (sP), alkaline phosphatase total activity (ALP), glucose, insulin, parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D], and urinary electrolytes corrected for creatinine (uNa/Cr, uK/Cr, uCl/Cr, uCa/Cr, and uP/Cr). Through the QUICKI index, we separated subjects with (IR+, n = 68) or without (IR-, n = 109) IR, and their parameters were compared. Associations were assessed by age-adjusted partial correlation, whose coefficients were compared by Fisher's transform.IR + had higher sP (3.54 ± 0.65 vs. 3.35 ± 0.47, p = 0.044) and lower uCa/Cr levels (0.073 ± 0.056 vs. 0.095 ± 0.072, p = 0.047) than IR-. BMI correlated with sP (r = 0.21, p < 0.05) and PTH (r = 0.29, p < 0.01). QUICKI negatively correlated with sCa (r = −0.22, p < 0.05) and positively with uCa/Cr (r = 0.21, p < 0.05), in turn correlating with uNa/Cr (r = 0.45, p < 0.001). In both groups, uCa/Cr correlated with eGFR and uNa/Cr (p < 0.05 to p < 0.001). In IR + only, sP correlated with BMI, PTH with insulin, and uP/Cr (p < 0.05 for all). IR+ and IR-coefficients differed (p < 0.05 to p < 0.001) for the correlation of sP with BMI and of PTH with insulin and uP/Cr. ConclusionThe higher sP and lower uCa/Cr levels found in men with IR + suggest that IR could modulate calcium-phosphate homeostasis, likely by affecting their renal handling.

Prediagnostic markers of insulin resistance and prostate cancer risk and death: A pooled study.

Insulin resistance has been shown to be related to a higher risk of several cancers, but the association with prostate cancer (PCa) has been inconsistent. We investigated prediagnostic markers of insulin resistance in men in four cohorts in Sweden, in relation to PCa risk (total, non-aggressive and aggressive) and PCa death using multivariable-adjusted Cox regression. The number of men, PCa cases and PCa deaths was up to 66,668, 3940 and 473 for plasma glucose and the triglyceride-glucose (TyG) index, and up to 3898, 586 and 102 for plasma insulin, glycated haemoglobin (HbA1c) and leptin. Higher HbA1c was related to a lower risk of non-aggressive PCa but no significant associations were found for insulin resistance markers with the risk of aggressive or total PCa. In PCa cases, higher glucose and TyG index were related to a higher risk of PCa death (hazard ratio [HR] per higher standard deviation, 1.22, 95% CI 1.00-1.49 and 1.24, 95% CI 1.00-1.55), which further increased when restricting the analyses to glucose and TyG index measures taken <10 years before the PCa diagnosis (HR, 1.70, 95% CI 1.09-2.70 and 1.66, 95% CI 1.12-2.51). No associations were observed for other markers in relation to PCa death. The results of this study showed no associations of insulin resistance markers with the risk of clinically relevant PCa, but higher glucose and TyG index were associated with poorer survival from PCa. The lack of association for other insulin resistance markers may be due to their smaller sample size.

The Effect of Eight Weeks of Concurrent Training on Serum Levels of Paraxonase-1, Irisin, Lipid Profile, and Insulin Resistance in Men With Metabolic Syndrome

Background: Irisin is a myokine suggested to exert anti-obesity benefits. On the other hand, paraxonase-1 (PON 1) is one of the most important free radical scavenging enzymes and is among the main protectors of lipoproteins against oxidizing compounds. This study aimed to evaluate the effect of 8 weeks of concurrent training on serum levels of irisin, PON 1, lipid profile, and insulin resistance in men with metabolic syndrome. Methods: In this quasi-experimental study, 30 men with metabolic syndrome (aged 25-35 years and with body mass&gt;25 kg.m-2) were purposefully selected and randomly divided into two groups of concurrent training (n=15) and control (n=15). Three sessions of the training program were held per week over an 8-week interval. Concurrent training included warm-up, resistance (20 minutes of resistance training), and endurance (25 minutes of activity on a stationary bike with an intensity of 50%-80% of maximum heart rate). Blood samples were collected before and 24 hours after exercise to measure serum levels of variables. Data were analyzed using independent and dependent t-tests. Results: At baseline, serum levels of PON 1, irisin, and high-density lipoprotein (HDL) were higher in the concurrent training group. The results of the study also indicated that 8 weeks of concurrent training significantly reduced the levels of insulin resistance, triglycerides (TG), cholesterol, low-density lipoprotein (LDL), systolic, and diastolic blood pressure in men with metabolic syndrome. Conclusion: Eight weeks of concurrent training improves the levels of irisin, insulin resistance, PON 1, and lipid profile of men with metabolic syndrome.

Osteocalcin is associated with triglyceride glucose index rather than HOMA-IR in men with type 2 diabetes.

The involvement of osteocalcin in the regulation of glucose tolerance in humans is controversial. We utilized a novel and practical insulin resistance surrogate, the triglyceride-glucose (TyG) index, to investigate the association between serum osteocalcin and insulin resistance in men with type 2 diabetes (T2D). This was a retrospective cross-sectional study that included 667 male patients suffering from T2D, with measurements of N-terminal mid-fragment of osteocalcin (N-MID), triglycerides (TG), fasting blood glucose (FBG) and C-peptide collected on the same day. We used the TyG index and HOMA-IR as surrogate measures for insulin resistance. Binary logistic regression models that adjust the sociodemographic characteristics and metabolism-related factors were used to assess the associations between osteocalcin and insulin resistance. Restricted cubic spline (RCS) analysis was used to test the potential non-linear relationship between N-MID and the risk of severe insulin resistance. Subgroup analysis evaluated the robustness of the association. N-MID was correlated with the level of insulin resistance when quantified by the TyG index in unadjusted and adjusted binary logistic regression models (all p < 0.05), but the relationship was not observed when assessed by HOMA-IR (all p > 0.05). RCS model further confirmed that the association between N-MID and the severe insulin resistance measured by the TyG index was non-linear (P = 0.047). Subgroup analysis showed that the association was detected only in younger patients with lower BMI and poorer glycemic control, without hypertension or smoking. Osteocalcin was inversely associated with the TyG index in men with T2D.

Prevalence rates of metabolic health and body size phenotypes by different criteria and association with insulin resistance in a Maltese Caucasian population

IntroductionHyperinsulinemia and insulin resistance are known to be associated with increased cardiovascular morbidity and mortality. A metabolically unhealthy phenotype is frequently used as a surrogate marker for insulin resistance. The aims of the current study were to compare the prevalence of the body size phenotypes using different definitions of metabolic health and to investigate which one of them is most strongly associated with insulin resistance in men and women.MethodsWe conducted a cross-sectional study in a middle-aged cohort of Maltese Caucasian non-institutionalized population. Metabolic health was defined using the various currently used definitions.ResultsThere were significant differences in the prevalence of body size phenotypes according to the different definitions. We also found significant sex differences in the predictive value of the various definitions of the metabolically unhealthy phenotype to predict insulin resistance. The strongest association was for the definition of having >2 NCEP-ATPIII criteria to characterize the metabolic unhealthy phenotype in women (odds ratio of 19.7). On the other hand, the Aguilar-Salinas et al. definition had the strongest association in men (odds ratio of 18.7).ConclusionsWe found large differences in the prevalence of the various body size phenotypes when using different definitions, highlighting the need for having standard criteria. Our data also suggest the need for sex-specific definitions of metabolic health.

Pomegranate juice intake enhances the effects of aerobic training on insulin resistance and liver enzymes in type 2 diabetic men: a single-blind controlled trial

BackgroundLifestyle interventions are the first-line treatment for Type 2 diabetes mellitus (T2DM), highly prevalent in the community. This study aimed to examine the 8-week separate and combined effects of aerobic training (AT) and pomegranate juice intake (PJI) on insulin resistance and serum levels of liver enzymes, liver enzymes, and insulin resistance in men with T2DM.MethodsThis study evaluated the alterations of anthropometric indices, insulin resistance, and liver enzymes in 40 middle-aged men (40–50) with T2DM. Participants were randomly assigned into four groups: AT+PJI (n = 10); AT (n = 10); PJI (n = 10), and control (C) (n = 10). The AT program consisted of 60–75% of maximum heart rate (HRmax), 40–60 min/day, and 3 days/wk. Participants in the PJI group consumed 240 ml of pomegranate juice (sugar or additive-free) daily for 8 weeks.ResultsAT+PJI, PJI, and AT groups decreased anthropometric indices, HOMA-IR, and liver enzymes after 8 weeks. In contrast, the C group significantly increased the mentioned variables after the intervention. The result showed that AT+PJI significantly lowered liver enzymes, anthropometric indices, and HOMA-IR than AT or PJI alone. Also, the results of this study showed no significant difference between AT and PJI groups. However, in these groups, significant improvements in these variables were observed compared to the control group.ConclusionDue to the effect of combined AT+PJI in improving T2DM risk factors, it could be recommended for T2DM patients to prevent increased liver enzymes and insulin resistance.

The Effect of Traditional Aerobic Exercise and Sprint Interval Training on Insulin Resistance in Men With Prediabetes: A Randomised Controlled Trial.

IntroductionPrediabetes is an intermediate stage with hyperglycaemia below the threshold of diabetes mellitus. Insulin resistance is a significant factor in its pathogenesis. Lifestyle modifications are suggested and found to be more beneficial in this stage. Moderate-intensity exercise for 30 to 45 minutes a day is routinely recommended but has low compliance, and lack of time is a significant deterrent. Sprint interval training (SIT) is an alternate exercise regimen with higher intensity and less time requirement. The present study compares the effect of a three-month intervention of traditional aerobic exercise and sprint interval training on insulin resistance in prediabetic men.MethodsThe study subjects were males aged 25 to 40 years with prediabetes as per the American Diabetes Association criteria of fasting and two-hour plasma glucose levels. The study is a parallel-group randomised trial with one arm (AE group) involved in the traditional aerobic exercise (brisk walking) for 30 minutes, five days a week. The other arm was the sprint interval training (SIT) group performing an ‘all-out’ run effort for one minute followed by a recovery rest period of one and a half minutes, completing one cycle of two and half minutes. Four such cycles were completed in each session. Thus, the exercise sessions were just 10 minutes daily, three days a week. The duration of the intervention was three months. One hundred and sixty participants were recruited after screening and randomly assigned in a 1:1 ratio to the two groups. The primary outcome measure was insulin resistance estimated by homeostasis model assessment -estimated insulin resistance (HOMA-IR). The secondary outcome measures were fasting plasma glucose and serum insulin, glycated haemoglobin, body mass index and waist-hip ratio.ResultsThe mean age of the AE group was 30.7 ± 3.3 years, and the SIT group was 31 ± 3.4 years. Seventy-two men from the AE group and 74 from the SIT group completed the study. After the three-month AE and SIT exercise, the per-protocol analysis reflected a significant reduction in insulin resistance, i.e., HOMA-IR (3.6 ± 1.1 to 3 ± 1.2, p<0.0001) after traditional aerobic exercise. Similarly, the HOMA-IR was significantly reduced after sprint interval training (3.3 ± 1.2 to 2.5 ± 1, p<0.0001). The intention-to-treat analysis also found that the reductions in HOMA-IR after both exercise protocols were statistically significant. The change in insulin resistance compared for the SIT vs AE group was not statistically significant. Secondary outcome measures HbA1c, fasting glucose, fasting insulin, BMI, and waist-hip ratio showed significant improvement with AE and SIT. ConclusionsThe sprint interval training similarly improved insulin resistance and other parameters compared to the traditional exercise group. SIT can be a time-efficient exercise protocol suggested as a part of lifestyle modification for men with prediabetes.

The Effects of Aerobic-Resistance Training and Broccoli Supplementation on Plasma Dectin-1 and Insulin Resistance in Males with Type 2 Diabetes.

Background: This study aimed to evaluate the effects of a combination of aerobic-resistance training (CARET) and broccoli supplementation on dectin-1 levels and insulin resistance in men with type 2 diabetes mellitus (T2D). Methods: Forty-four males with T2D were randomly allocated to four groups (n = 11 each group): CARET + broccoli supplement (TS), CARET + placebo (TP), control + broccoli supplement (S), and control + placebo (CP). CARET was performed three days per week for 12 weeks. TS and S groups received 10 g of broccoli supplement per day for 12 weeks. All variables were assessed at baseline and 12 weeks. Results: Plasma dectin-1 levels were decreased in TS and TP groups compared with the CP group (p < 0.05). Cardiometabolic risk factors showed significant reductions in TP and TS groups compared to S and CP groups (p < 0.05). Conclusion: The combination of CARET and broccoli supplementation produced the largest improvements in insulin resistance and dectin-1 and other complications of T2D.

Рівень прозапальних лімфокінів і гормонів у чоловіків, хворих на цукровий діабет 2-го типу

Актуальність. Відомо, що розвиток інсулінорезистентності (ІР), основного чинника метаболічного синдрому (МС), супроводжується дисбалансом у системі цитокінів: підвищенням рівня інтерлейкіну-6 (ІЛ-6), фактора некрозу пухлини α (ФНП-α) та зниженням ІЛ-10, ІЛ-4. Однією з причин інсулінорезистентності у чоловіків може бути зменшення продукції тестостерону, оскільки його достатня кількість посилює чутливість до інсуліну. Мета дослідження: визначити рівні прозапальних лімфокінів і гормонів у хворих на цукровий діабет (ЦД) 2-го типу з МС та андрогенним дефіцитом. Матеріали та методи. Обстежені 76 чоловіків віком від 35 до 68 років (29 — з МС та 47 — хворих на ЦД 2-го типу). Рівні прозапальних лімфокінів, естрадіо­лу, тестостерону вільного та загального визначали у сироватці крові радіоімунним методом, рівні ФНП-α, ІЛ-6, лептину — імуноферментними методами. ІР визначали за індексом НОМА. Діагноз МС встановлювали на підставі критеріїв АТР III — NCEP. У контрольну групу (n = 21) ввійшли умовно здорові люди. Результати. У хворих на ЦД 2-го типу з МС та у групі з МС без ЦД були підвищені рівні ФНП-α й ІЛ-6, кортизолу, альдостерону, адренокортикотропного гормону (АКТГ) та інсуліну. Проведені дослідження показали наявність андрогенного дефіциту в усіх групах пацієнтів. Більш виражені ознаки андрогенного дефіциту спостерігали в обстежених чоловіків із МС та ЦД 2-го типу. Рівень інсуліну й АКТГ прямо пропорційно залежить від індексу маси тіла. У пацієнтів із МС без ЦД спостерігалася лише тенденція до підвищення рівня лептину. Встановлена тенденція підвищення рівня естрадіолу у чоловіків з ЦД 2-го типу та МС. Висновки. Отримані результати відповідають гіпотезі щодо визначальної ролі прозапальних цитокінів імунної системи у генезі ЦД 2-го типу. У даному випадку причиною розвитку ЦД є дисфункція не жирової тканини, а неспецифічної ланки імунітету.

National trends in insulin resistance and β-cell dysfunction among adults with prediabetes: NHANES 2001–2016

BackgroundInsulin resistance is the central abnormality and mechanism underlying the progression of cardiometabolic-based chronic diseases. This study aimed to evaluate the trends in insulin resistance and β-cell dysfunction from 2001 to 2016 among US adults with undiagnosed diabetes, prediabetes, and normal glucose regulation and to provide sex-specific information using data from National Health and Nutrition Examination Surveys (NHANES) 2001–2016. MethodsData from 14,481 participants aged over 20 years from 8 consecutive 2-year cross–sectional cycles of the NHANES from 2001 to 2016 were used. Updated homoeostasis model assessment 2 (HOMA2: HOMA2%B for β-cell function and HOMA2IR for insulin resistance) was used as a surrogate measure. We defined the upper sex-specific tertile of HOMA2IR as insulin resistance and the lower corresponding tertile of HOMA2%B as low β-cell function. ResultsIn both sexes with undiagnosed diabetes, HOMA2%B (men, Ptrend = 0.118; women, Ptrend = 0.184) and HOMA2IR (men, Ptrend = 0.710; women, Ptrend = 0.855) remained stable over time. In the prediabetes group, both sexes exhibited significant increasing trends in HOMA2%B (men, Ptrend < 0.010; women, Ptrend < 0.010) and HOMA2IR (men, Ptrend < 0.010; women, Ptrend < 0.050). Adjusting for waist circumference mildly attenuated the trend in HOMA2IR and insulin resistance in men (Ptrend < 0.010), but it resulted in no significance in women (Ptrend = 0.196). In regard to normal glucose regulation, both sexes presented significant decreasing trends in low β-cell function (men, Ptrend < 0.050; women < 0.010) and attenuated trends in insulin resistance (men, Ptrend = 0.196; women, Ptrend = 0.121). ConclusionsOver 16 years, insulin resistance demonstrated an increasing trend in adult US population with prediabetes, while β-cell function showed a compensatory increasing trend. Identifying people with prediabetes early and focusing on reducing insulin resistance as the intervention core, especially controlling central obesity, might increase the opportunity for cardiovascular and diabetes risk reduction.

Zoledronic acid does not affect insulin resistance in men receiving androgen deprivation therapy: a prespecified secondary analysis of a randomised controlled trial.

Background:Animal studies suggest that undercarboxylated osteocalcin may improve insulin sensitivity via its effect on testicular testosterone production. Human studies have been conflicting. Men undergoing androgen deprivation therapy (ADT) for prostate cancer experience profound hypogonadism resulting in increased insulin resistance. In a randomised controlled trial (RCT) of zoledronic acid versus placebo in men commencing extended-duration ADT, we aimed to examine the effects on fat mass and glucose metabolism. We hypothesised that zoledronic acid, which reduces osteocalcin concentrations, would worsen ADT-induced insulin resistance.Methods:This was a prespecified secondary analysis of an RCT designed to evaluate the effects of zoledronic acid on bone microarchitecture in 76 men with non-metastatic prostate cancer undergoing curative radiotherapy combined with adjuvant ADT (n = 39 randomised to a single dose of zoledronic acid 5 mg, n = 37 randomised to matching placebo). Oral glucose tolerance tests to determine Matsuda Index were performed at 0, 3, 12 and 24 months. Using a mixed model, mean adjusted differences [MAD (95% confidence interval)] between the groups over time are reported.Results:Over 24 months of ADT, fat mass increased and lean mass decreased for both groups, with no significant between group difference [MAD 401 g (−1307; 2103), p = 0.23 and −184 g (−1325; 955), p = 0.36 respectively]. Bone remodelling markers C-telopeptide [MAD −176 ng/l (−275; −76), p < 0.001 and P1NP −18 mg/l (−32; −5), p < 0.001] as a surrogate for osteocalcin, remained significantly lower in the zoledronic acid group, compared with placebo. There was no mean adjusted between-group difference for homeostatic model assessment 2 insulin resistance (HOMA2-IR) [−0.2 (−0.6; 0.2), p = 0.45], HbA1c [−0.1% (−0.3; 0.1), p = 0.64] or Matsuda Index [0.8 (−1.1; 2.7), p = 0.38]. The Matsuda Index decreased in both groups consistent with worsening insulin resistance with ADT.Conclusion:A single dose of zoledronic acid does not appear to influence glucose metabolism in men newly commencing ADT. Further study to evaluate the endocrine relationship between bisphosphonates, bone and glucose metabolism is required.Trial Registration Number:[ClinicalTrials.gov identifier: NCT01006395].

New opportunities for the correction of non-alcoholic fatty liver disease in men with type 2 diabetes mellitus and hypogonadism

Background: The common pathogenetic relations of type 2 diabetes mellitus (T2DM), testosterone (T) deficiency and non-alcoholic fatty liver disease (NAFLD) have indicated a new direction in the study of their mutual influence. It was found that NAFLD is more pronounced in men with T2DM and hypogonadism than in eugonadal patients and associated with hyperinsulinemia, insulin resistance, impaired lipid metabolism and adipose tissue dysfunction. However, the effects of testosterone replacement therapy (TRT) on the severity of NAFLD in men with hypogonadism have not been studied.Aims: To study the effect of TRT on the severity of NAFLD in men with T2DM and hypogonadism.MATERIALS AND METHODS: Anthropometric data, biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGTP), glucose, immunoreactive insulin, HOMA index, glycosylated hemoglobin, lipidogram), ELISA analysis (total T, LH, sex hormone binding globulin, resistin, adiponectin, leptin), as well as magnetic resonance imaging with determination of the liver fat fraction were examined.Results: The study included 60 men with T2DM and hypogonadism (mean age 54 [49; 57] years), who were randomized into 2 groups: 1 (n=30) - patients who received 1% transdermal T gel (50 mg/day) in addition to standard hypoglycemictherapy; 2 (n=30) - patients who received standard hypoglycemic therapy. The follow-up period was 6 months. T therapy was associated with a decrease in liver enzyme levels: AST by 31%, ALT by 21%, and GGTP by 15.9% (p&lt;0.05) and the hepatic fat fraction by 1.7 times, which reflect the regress of liver inflammation, and, consequently, a decrease in the severity of NAFLD. Moreover, TRT has improved the function of adipose tissue - reduced the concentration of leptin by 1.4 times and resistin by 1.5 times, which was accompanied by an increase in adiponectin level by 1.3 times (p&lt;0.01). The use of TRT was associated with decrease in the severity of visceral obesity, hyperinsulinemia by 1.5 times, an insulin resistance index HOMA by 2.2 times, fasting glycaemia and HbA1c levels, despite constant hypoglycemic therapy. Statistically significant decrease in the levels of total cholesterol and triglycerides was observed in men receiving TRT. Thus, a decrease in adipose tissue dysfunction and insulin resistance in men receiving TRT can be considered as a pathogenetic mechanism responsible for improving liver function and reducing the severity of NAFLD.Conclusions: TRT in men with T2DM and hypogonadism is accompanied by regress of inflammatory activity in liver and intensity of hepatocytes steatosis, reflected by decrease in liver enzymes levels and liver fat fraction.

Type 2 diabetes risk gene Dusp8 regulates hypothalamic Jnk signaling and insulin sensitivity.

Recent genome-wide association studies (GWAS) identified DUSP8, encoding a dual-specificity phosphatase targeting mitogen-activated protein kinases, as a type 2 diabetes (T2D) risk gene. Here, we reveal that Dusp8 is a gatekeeper in the hypothalamic control of glucose homeostasis in mice and humans. Male, but not female, Dusp8 loss-of-function mice, either with global or corticotropin-releasing hormone neuron-specific deletion, had impaired systemic glucose tolerance and insulin sensitivity when exposed to high-fat diet (HFD). Mechanistically, we found impaired hypothalamic-pituitary-adrenal axis feedback, blunted sympathetic responsiveness, and chronically elevated corticosterone levels driven by hypothalamic hyperactivation of Jnk signaling. Accordingly, global Jnk1 ablation, AAV-mediated Dusp8 overexpression in the mediobasal hypothalamus, or metyrapone-induced chemical adrenalectomy rescued the impaired glucose homeostasis of obese male Dusp8-KO mice, respectively. The sex-specific role of murine Dusp8 in governing hypothalamic Jnk signaling, insulin sensitivity, and systemic glucose tolerance was consistent with functional MRI data in human volunteers that revealed an association of the DUSP8 rs2334499 risk variant with hypothalamic insulin resistance in men. Further, expression of DUSP8 was increased in the infundibular nucleus of T2D humans. In summary, our findings suggest the GWAS-identified gene Dusp8 as a novel hypothalamic factor that plays a functional role in the etiology of T2D.

Clinical Features and Insulin Resistance in Men with a Metabolically Unhealthy Obesity Phenotype

Purpose of the study: The aim of study was to analyze the characteristics of hormonal-metabolic parameters in men with a metabolically unhealthy obesity phenotype; identify the value of special indicators for diagnosis of insulin resistance.Materials and methods: The examination included 108 patients with body mass index ≥25 kg/m2, which were hospitalized. According to the current national guidelines for the diagnosis and treatment of obesity, all examined patients were divided into 2 groups: 1 — with metabolically healthy obesity phenotype, 2 — with metabolically unhealthy obesity phenotype. The study presents the results of comparative simultaneous nonrandomized study of two groups with using of different methods of examination (anthropometric indicators, laboratory tests for inspection of the hormonal profile, biochemistry parameters, and calculation of TyG index for diagnosis of insulin resistance).Results and discussion: The study found that patients of working age with metabolically unhealthy obesity phenotype are characterized by unfavorable anthropometric and hormonal-metabolic parameters and more severe polymorbid pathology (first of all cardiovascular diseases). The results of study revealed the value of special indicators for the diagnosis of insulin resistance (visceral obesity index &gt;1,85; TyG &gt;3,98; fat mass &gt;30,1).Conclusion: timely detection of insulin resistance indicators has great importance and practical application due to simplicity and accessibility.

Changes in SFRP5, WNT5A, HbA1c, BMI, PBF, and insulin resistance in men with type 2 diabetes after 12 weeks of combined exercise (HIIT and resistance)

Secreted frizzled-related protein 5 (SFRP5) and WNT family member 5A (WNT5A) have been found to associate with glucose metabolism and insulin sensitivity through noncanonical WNT signaling. The purpose of this study was to investigate changes in SFRP5, WNT5A, glycated hemoglobin (HbA1c), body mass index (BMI), percentage body fat (PBF), and insulin resistance in men with type 2 diabetes after 12 weeks of combined exercise (high-intensity interval training (HIIT) and resistance) and examine the relationship between these variables in men with type 2 diabetes. Nineteen men with type 2 diabetes (mean age of 58.3) were divided into two groups: experimental group (10 individuals) and control group (9 individuals). The experimental group performed 12 weeks of combined exercise (HIIT and resistance). Twelve weeks of combined exercise (HIIT and resistance) increased SFRP5 serum level and decreased WNT5A serum level, HbA1c, insulin resistance, BMI, and PBF in the intervention group compared with the control group. SFRP5 had a significant negative relationship with WNT5A, insulin resistance, BMI, and PBF. In addition, BMI had a significant positive relationship with WNT5A, insulin resistance, and PBF. The improvement of type 2 diabetic men’s health can be a result of increased anti-inflammatory factor SFRP5 and decreased inflammatory factor WNT5A through reduction of BMI and PBF. IRCT20151026024717N3

Association between the Thigh Muscle and Insulin Resistance According to Body Mass Index in Middle-Aged Korean Adults.

BackgroundWe examined the associations between thigh muscle area (TMA) and insulin resistance (IR) according to body mass index (BMI) in middle-aged Korean general population.MethodsTMA was measured using quantitative computed tomography and corrected by body weight (TMA/Wt) in 1,263 men, 788 premenopausal women, and 1,476 postmenopausal women all aged 30 to 64 years. The tertiles of TMA/Wt were calculated separately for men and for premenopausal and postmenopausal women. Homeostatic model assessment for insulin resistance (HOMA-IR) was performed using fasting blood glucose and insulin levels, and increased IR was defined according to sex-specific, top quartiles of HOMA-IR. Associations between the TMA/Wt tertiles and increased IR according to the BMI categories (<25 and ≥25 kg/m2) were assessed using multivariable logistic regression analysis.ResultsIn men with higher BMIs, but not in those with lower BMIs, the presence of an increased IR had significantly higher odds ratios in the lower TMA/Wt tertiles, even after adjustment for visceral fat area. However, in premenopausal and postmenopausal women, there was no significant inverse association between TMA/Wt tertiles and increased IR, regardless of BMI category.ConclusionOur findings suggest that the thigh muscle is inversely associated with IR in men, particularly in those with higher BMIs.

Effects of 12 weeks of combined aerobic-resistance exercise training on levels of chemerin, omentin and insulin resistance in men with type 2 diabetes

Effects of 12 weeks of combined aerobic-resistance exercise training on levels of chemerin, omentin and insulin resistance in men with type 2 diabetes