Changes In Fasting Insulin Levels Research Articles

The effect of low volume high-intensity interval training on metabolic and cardiorespiratory outcomes in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

The present systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effect of low volume high-intensity interval training (LVHIIT) on the metabolic and cardiorespiratory outcomes in patients with type 2 diabetes mellitus (T2DM). Relevant articles were sourced from PubMed, EBSCO, Web of Science, Embase, and the Cochrane Library from inception to October 2022. The study search strategy and all other processes were implemented in accordance with the PRISMA statement. Five randomized controlled trials that satisfied the inclusion criteria were included in this meta-analysis. The LVHIIT group had significantly lower fasting blood glucose levels (RR= -1.21; 95% CI= -2.02- -0.40, p = 0.0032) and HbA1c levels (RR= -0.65; 95% CI= -1.06- -0.23, p = 0.002) and higher levels of insulin resistance indicator HOMA-IR (RR= -1.34; 95% CI = -2.59- -0.10, p = 0.03) than the control group. Moreover, our results show that LVHIIT can reduce body mass (RR = -0.94, 95% CI = -1.37- -0.51, p<0.0001) and body mass index (RR = -0.31, 95% CI = -0.47- -0.16, p<0.0001). LVHIIT had a better therapeutic effect on blood lipid metabolism, such as total cholesterol, high-density lipoprotein, low-density lipoprotein and triglycerides. However, the change in fasting insulin levels was not statistically significant (RR= -1.43; 95% CI = -3.46- 0.60, p =0.17). Furthermore, LVHIIT reduced the systolic blood pressure (RR =-4.01, 95% CI = -4.82 - -3.21, p<0.0001) and improved peak oxygen uptake (VO2peak) compared to the control group (RR= 5.45; 95% CI = 1.38 - 9.52, p =0.009). After a certain period of LVHIIT, glycaemic control, insulin resistance, body weight, lipid profile and cardiorespiratory outcomes were significantly improved in T2DM patients.

High blood pressure mediated the effect of fasting insulin level on nonalcoholic fatty liver disease risk: A Mendelian randomization study.

The interactions between fasting insulin levels, high blood pressure and nonalcoholic fatty liver disease (NAFLD) are still unclear. We examined the causal mechanisms between these three cardiometabolic traits using Mendelian randomization (MR) approach by utilizing genetic instruments. Three different genome-wide association studies resources of European ancestry were utilized for the present study. Two-sample MRs were used to assess causal effects between fasting insulin levels, high blood pressure and NAFLD. Multivariate MR was used to calculate the mediating effect. The inverse variance-weighted method was used as the main analysis method. Our study confirmed a causal effect of fasting insulin levels (IVW-OR = 9.54, P = 0.001) and high blood pressure (IVW-OR = 3.926, P = 0.005) on NAFLD risk. And fasting insulin level was positively casually associated with high blood pressure risk (IVW-OR = 1.170, P < 0.001). However, the impact of high blood pressure on fasting insulin levels was still uncertain because of the presence of horizontal pleiotropy. Reverse MR showed NAFLD had a positive correlation with fasting insulin levels (IVW-OR = 1.010, P < 0.001) and a negative causal effect on high blood pressure risk (IVW-OR = 0.997, P = 0.037). Combined the multivariate MR result revealed high blood pressure partially mediated the contribution of fasting insulin level to NAFLD risk (proportion mediated: 9.091%). Our study suggests there is a bidirectional causal relationship between fasting insulin levels and NAFLD. High blood pressure seems to play a mediating role in the development of NAFLD caused by changes in fasting insulin levels. However, it is uncertain whether high blood pressure is a mediator between NAFLD and the risk of fasting insulin level.

RF34 | PMON276 The Effect of Gender Affirming Hormone Therapy (GAHT) on Non-Conventional Cardiovascular Risk Markers in Transgender Men: A Systematic Review

Abstract The process of gender transitioning includes the employment of gender-affirming hormone therapy (GAHT) to attenuate gender dysphoria. Although considered relatively safe, there is still debate whether GAHT may increase the risk of cardiovascular disease (CVD) in transgender men (TM). Non-conventional subclinical cardiovascular (CV) risk markers, such as inflammation or coagulation markers, endothelial activity-related substances, and the use of ultrasound-assisted vascular function evaluation, may improve CV risk prediction in specific populations. Therefore, we conducted a systematic review to summarize the available findings regarding GAHT and its effects on these non-conventional cardiovascular risk markers in TM. Medline, LILACS, SCOPUS, and Embase databases were searched for cross-sectional, case-control, cohort, or randomized clinical trial studies published until July 2020. The selection criteria for the studies were as follows: ≥ 18 years old transgender male, no established CVD, using GAHT (androgens) for at least 2 months and compared with cis women or untreated transmen or before and during/after treatment for cohort studies. From 152 studies initially identified, 7 studies (3 cohorts and 4 case-control) were included in the systematic review. Some of these studies assessed different CV risk markers in the same group of participants. No changes were found in t-PA PAI-1, ICAMs, and PCR-us after 4 and 12 months of GAHT. Fibrinogen did not differ either in TM with or with no GAHT. Three studies evaluated flow-mediated-vasodilation (FMD) of the brachial artery. The only cohort study found no changes in FMD after 12 months of GAHT. One case-control study observed significant impaired FMD, and another one showed impaired FMD- after-nitroglycerin in transmen compared with cis women. One study reported increased homocysteine and higher carotid intima-media thickness (C-MIT) after 12 months of hormone use. Further, one study observed testosterone did not affect distensibility (DC) or compliance (CC) coefficient after 12 months, but the changes in fasting insulin levels were negatively associated with changes in the CC and DC. One study assessed the vascular function using brachial-ankle pulse wave velocity (baPWV) and observed a higher risk in TM with GAHT versus the untreated group. The results of the present systematic review suggest that GAHT may be associated with worse subclinical cardiovascular markers in TM. Further studies assessing long-term clinical follow-up of transgender men using GAHT could positively impact the prevention of CVD and management strategies for this population. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.

Follow-up Evaluation of Association between Weight Changes, Metabolic, and Hormonal Outcomes in Children - a Single-center PilotStudy.

Fasting blood glucose, insulin level, and lipid profile are the minimal tests according to the Romanian guidelines to evaluate obese children. Cross-sectional studies for pediatric obesity in Romania focused only on epidemiology and management. Our study aimed to evaluate the metabolic and hormonal changes in association with follow-up bodyweight modifications. Medical charts of overweight or obese children presenting at the First Paediatric Hospital, Cluj-Napoca from January 2017 to March 2019 were retrospectively evaluated. Anthropometric measures [e.g., body mass index (BMI), and waist circumference] and blood tests such as inflammatory markers (e.g., white blood cell and neutrophil absolute/relative counts, C-reactive protein), metabolic parameters (e.g., liver enzymes, uric acid, fasting blood glucose, triglycerides, high-density lipoprotein-cholesterol), fasting blood insulin, and cortisol levels were evaluated. Twenty-two overweight or obese children (17 girls, median age of 13 years) monitored on median for 7.5 months were in-cluded in the study. Blood glucose level significantly decreased (p=0.010) and fasting insulin levels increased (p=0.051) at follow-up evaluation, independently of BMI-for-age z-score. Fasting insulin levels were associated with waist circumference (Spearman's rank cor-relation coefficient) ρ=0.58, p=0.030). BMI-for-age z-score proved to be associated with the C-reactive protein level at baseline (ρ=0.70, p=0.036, n=9) and high-density lipoprotein cholesterol at follow-up (ρ=-0.52, p=0.033, n=17). Present analysis found changes in fasting insulin levels in relation to the abdominal circumference and high-density lipoprotein cholesterol and C-reactive protein levels in relation to BMI-for-age z-score in obese children.

S90. A SYSTEMATIC REVIEW AND META-ANALYSIS OF PHARMACOLOGICAL INTERVENTIONS FOR REDUCTION OF WEIGHT GAIN IN PEOPLE WITH SCHIZOPHRENIA: 2019 UPDATE

BackgroundWeight gain and obesity are common problems encountered by patients with schizophrenia. This is partially attributable to use of second-generation antipsychotics that are associated with weight gain and other metabolic disturbances. The significance of this prevalence and its impact on premature mortality and morbidity requires better consensus on its management. The objective of this review is to determine the effects of adjunctive pharmacological interventions aimed at reducing weight gain in schizophrenia.MethodsWe searched the Cochrane Schizophrenia Group’s Trials Register which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. Inclusion criteria consisted of all randomized controlled trials examining any adjunctive pharmacological intervention for weight loss in patients with schizophrenia or schizophrenia-like illnesses. The primary outcome of each study had to be body weight or a weight related measure. We reliably selected, quality assessed, and extracted data from studies. As endpoint and change data was combined in the analysis, mean differences (MD) of the change from baseline were calculated using Review Manager 5.3.ResultsSixty-one randomized controlled trials met inclusion criteria for this review (pooled n = 3328). Metformin is effective in bringing about modest weight loss (Weight: MD -3.40 kg, 95% CI -4.63 to -2.16; participants = 731; studies = 12; BMI: MD -1.39, 95% CI -1.94 to -0.85; participants = 879; studies = 13). Heterogeneity was reduced by dividing populations into first episode psychosis (FEP) and chronic populations, where FEP patients appeared to benefit most from early metformin intervention (Weight: MD -5.18 kg, 95% CI -6.22 to -4.14; BMI: MD -1.87 kg/m2, 95% CI -2.19 to -1.56; participants = 214; studies = 3) as compared to chronic patients (Weight: MD -2.22 kg, 95% CI -3.07 to -1.37; participants = 517; studies = 9; BMI: MD -1.18 kg/m2, 95% CI -1.89 to -0.48; participants = 665; studies = 10). However, ethnicity could be a confounder for the apparent effect of illness stage, as all first episode metformin intervention studies were conducted in patients with Chinese ethnicity. Metformin as a treatment for weight gain may be associated with additional adaptive changes in fasting insulin levels and insulin resistance. The frequency of adverse effects did not differ between metformin and placebo groups. Moreover, glucagon-like peptide agonists (GLP-1RAs), such as liraglutide and exenatide, were also effective in reducing weight (Weight: MD -3.95 kg, 95% CI -7.08 to -0.83; participants = 165; studies = 3; BMI -1.26 kg/m2, 95% CI -2.21 to -0.30; participants = 165; studies = 3; waist circumference: MD -3.25, 95% CI -5.93 to -0.57; participants = 165, studies = 3). The frequency of adverse effects did not differ between GLP-1RA and placebo groups. Topiramate 200 mg was also effective for weight reduction (Weight: MD=-6.61 kg, 95% CI -9.62 to -3.61; BMI: MD=-2.72, 95% CI -3.25 to -2.20; participants = 181, studies = 3).DiscussionThis review highlights the promise of pharmacological interventions for decreasing weight gain associated with antipsychotic use. Of the drugs studied, metformin has the most evidence and was most effective in bringing about modest weight loss. Topiramate and GLP-1RA also have accumulating evidence supporting efficacy in reducing weight. Interpretation for other agents is limited by the small number of studies, sample size, and short study duration. Future studies that are adequately powered, with longer treatment duration, will be needed in evaluating the efficacy and safety of interventions for managing weight gain further.

Randomized Phase II Trial of Exercise, Metformin, or Both on Metabolic Biomarkers in Colorectal and Breast Cancer Survivors.

BackgroundObservational data support inverse relationships between exercise or metformin use and disease outcomes in colorectal and breast cancer survivors, although the mechanisms underlying these associations are not well understood.MethodsIn a phase II trial, stage I–III colorectal and breast cancer survivors who completed standard therapy were randomly assigned to structured exercise or metformin or both or neither for 12 weeks. The primary outcome was change in fasting insulin levels; secondary outcomes included changes in other blood-based energetic biomarkers and anthropometric measurements. Analyses used linear mixed models.ResultsIn total, 139 patients were randomly assigned; 91 (65%) completed follow-up assessments. Fasting insulin levels statistically significantly decreased in all three intervention arms (−2.47 μU/mL combination arm, −0.08 μU/mL exercise only, −1.16 μU/mL metformin only, + 2.79 μU/mL control arm). Compared with the control arm, all groups experienced statistically significant weight loss between baseline and 12 weeks (−1.8% combination arm, −0.22% exercise only, −1.0% metformin only, +1.55% control). The combination arm also experienced statistically significant improvements in the homeostatic model assessment for insulin resistance (−30.6% combination arm, +61.2% control) and leptin (−42.2% combination arm, −0.8% control), compared with the control arm. The interventions did not change insulin-like growth factor–1 or insulin-like growth factor binding protein–3 measurements as compared with the control arm. Tolerance to metformin limited compliance (approximately 50% of the participants took at least 75% of the planned dosages in both treatment arms).ConclusionsThe combination of exercise and metformin statistically significantly improved insulin and associated metabolic markers, as compared to the control arm, with potential greater effect than either exercise or metformin alone though power limited formal synergy testing. Larger efforts are warranted to determine if such a combined modality intervention can improve outcomes in colorectal and breast cancer survivors.

Impact of 3-year changes in fasting insulin and insulin resistance indices on incident hypertension: Tehran lipid and glucose study

BackgroundTo examine the association between changes in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin-glucose ratio (IGR) levels, over approximately 3 years with incident hypertension.MethodsA total of 2814 Iranian participants (1123 men) without hypertension and known diabetes at baseline and the first examination were followed for a median of 6.32 years. The associations between quartiles of changes in fasting insulin and IR indices with incident hypertension were assessed using multivariate Cox proportional hazard regression analyses with first quartile as reference. The models were adjusted for baseline values of insulin or each IR index, and age, sex, smoking, physical activity, educational levels, marital status, history of cardiovascular diseases, baseline levels of systolic and diastolic blood pressures, estimated glomerular filtration rate, triglycerides, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose (only for insulin change) and both body mass index (BMI) per se, and its change. Akaike’s information criteria (AIC) was applied as indicator for goodness of fit of each predictive model. The discrimination ability of models was calculated using the Harrell’s C statistic.ResultsDuring the study, 594 incident cases of hypertension (253 men) were identified. The 4th quartile of changes in insulin, HOMA-IR, and IGR showed hazard ratios (95% confidence interval) of 1.31 (1.01–1.69), 1.18 (0.92–1.52), and 1.53 (1.18–1.98) for hypertension, respectively, in fully-adjusted models. Changes in fasting insulin levels and IR indices showed significant increasing trends for incident hypertension, moving from 1st to 4th quartiles (all P-values < 0.05). Focusing on model fitness, no superiority was found between changes in fasting insulin, HOMA-IR, and IGR to predict incident hypertension. The discriminatory powers of changes in fasting insulin and IR indices as assessed by C index were similar (i.e. about 80%).ConclusionChanges in fasting insulin and IR indices were significantly associated with developing hypertension among normotensive population even after considering BMI changes.

1131-P: Endoscopic Duodenal Submucosal Laser Ablation for the Treatment of Type 2 Diabetes Mellitus: Results of First-in-Human Pilot Study

The duodenum has recently emerged as a key regulator in glucose metabolism via modulation of a complex network of neural and hormonal signals in response to ingested food. DiaGone™ is an endoscopic device which utilizes precisely controlled laser technology to target the duodenal submucosal neural plexi with the aim of improving glucose control by modulating the gastrointestinal neurohumoral axis. Nine subjects (5 males) with obesity (BMI 34.0 ± 4.6 kg/m2) and type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin were included in this first-in-human trial in order to assess the efficacy and safety of DiaGone™. Subjects were instructed to continue with regular diet 24h after the procedure and metformin dose was not changed during the study period. Biochemical and anthropometric parameters were assessed at baseline and 3 and 6 months after the procedure and continuous glucose monitoring (CGM) and a standard liquid meal test were performed at baseline and 3 months after the procedure. DiaGone™ significantly decreased HbA1C from 78.3 ± 13.3 mmol/mol at baseline to 64.9 ± 6.4 mmol/mol and 64.8 ± 7.1 mmol/mol at 3 and 6 months, respectively (p&amp;lt;0.01). Similarly, a decrease in fasting glucose levels was noted (12.4 ± 3.5 vs. 9.5 ± 2.0 vs. 9.7 ± 2.7 mmol/l, p&amp;lt;0.01) with no significant changes in fasting insulin levels. Glucose AUC during the 150 min meal test 3 months after the procedure showed a reduction of 20% from baseline (43,435 vs. 34,096, p&amp;lt;0.01). No significant changes were observed in AUC for insulin. No adverse events related to the procedure or significant changes in weight were reported throughout the 6-month period. In conclusion, these pilot results suggest that endoscopic duodenal submucosal laser ablation using the DiaGone™ device is associated with improvements in both baseline and postprandial glycemia as well as HbA1C with no significant changes in insulin levels or body weight while having a favorable safety and tolerability profile. Disclosure M. Mraz: None. I. Marcovitch: Employee; Self; Digma Medical. I. Lankova: None. H. Kratochvilova: None. A. Cinkajzlova: None. M. Benes: None. J. Korner: Board Member; Self; Digma Medical. Stock/Shareholder; Self; Digma Medical. Z. Vlasakova: None. J. Spicak: None. T. Pelikanova: None. M. Haluzik: None. Funding MH CZ - DRO; Institute for Clinical and Experimental Medicine (IN00023001); RVO (VFN64165)

Effect of a Novel High Fiber Rice Diet on 24-Hour Glycemic Responses in Asian Indians Using Continuous Glucose Monitoring: A Randomized Clinical Trial.

We have recently demonstrated a medium glycemic index for novel high fiber white rice (HFWR) variety compared to regular white rice (RWR). However, substituting HFWR for RWR during the whole day's diet may provide extended benefits. The current study aims to assess the 24 h glycemic responses of a HFWR diet compared to a RWR diet. Continuous glucose monitoring (CGM) was used to assess the glycemic profile in 18 overweight, non-diabetic Asian Indians aged 25 to 50 in a randomized cross-over design. The volunteers were provided with iso-caloric (≈2100 kcal/day) HFWR or RWR based diets for four continuous days and switched diets after appropriate washout. Fasting blood samples for insulin assessments were collected at baseline and at the end of 4 day feeding. The glucose response in terms of incremental area under the curve (IAUC) was recorded. General linear model was used to assess the adjusted mean change of fasting insulin level of HFWR compared to RWR. Age and sex were adjusted as confounders in the model. The average 24 h glucose response for HFWR was significantly lower (IAUC 66.3 ± 3.1 mg-5 min/dL) than RWR (IAUC 79.8 ± 5.7 mg-5 min/dL). The adjusted mean change in fasting insulin levels from baseline was also lower for HFWR compared to RWR. HFWR elicited a 34% and 30% lower 24 h glycemic and insulin response respectively, compared to RWR. Replacing RWR with HFWR may be a healthier alternative for Asian Indians who are at a higher risk of developing type 2 diabetes.

Association between Changes in Anthropometric Indices and in Fasting Insulin Levels among Healthy Korean Adolescents: The JS High School Study.

BackgroundThis study investigated the association between changes in anthropometric indices and fasting insulin levels among healthy adolescents and whether the association differed by baseline obesity status.MethodsThis analysis was based on data collected for the JS High School study; 884 healthy adolescents aged 15 to 16 years followed up for 24 to 30 months were included. Changes in anthropometric indices and fasting insulin levels were computed as the difference between baseline and follow-up values. Multivariate linear regression models were used to determine the association between changes in anthropometric indices and fasting insulin levels. Based on body mass index (BMI)-for-age and waist circumference (WC)-for-age percentiles, participants were classified as normal weight (<85th percentile), overweight (85th percentile to <95th percentile), or obese (≥95th percentile).ResultsChanges in BMI, WC, waist-hip ratio, and waist-height ratio were significantly associated with changes in fasting insulin levels in both sexes (P<0.05). In analyses stratified by baseline obesity status, the association between change in BMI and change in fasting insulin was significantly stronger in overweight (males: standardized β=1.136; females: standardized β=1.262) and obese (males: standardized β=1.817; females: standardized β=2.290) participants than in those with normal weight (males: standardized β=0.957; females: standardized β=0.976) at baseline. Results were similar for changes in WC.ConclusionChanges in anthropometric indices were positively associated with fasting insulin level increases. Moreover, those who were overweight or obese at baseline had a higher absolute increase in fasting insulin levels per one standard deviation unit increase in anthropometric indices than adolescents with normal weight.

Association of the rs10830963 polymorphism in melatonin receptor type 1B (MTNR1B) with metabolic response after weight loss secondary to a hypocaloric diet based in Mediterranean style

Some genetic variants within MTNR1B were related with fasting glucose levels or the increased prevalence of diabetes mellitus and obesity. The aims of the present investigation were to determine the influence of rs10830963 MTNR1B variant in relation to body weight loss, insulin resistance and adipokine levels in response to a hypocaloric diet with Mediterranean pattern. A Caucasian population of 80 obese patients was studied before and after 12 weeks on a hypocaloric diet. Body weight, fat mass, waist circumference, blood pressure, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipoprotein levels and adipocytokines levels (leptin, adiponectin and resistin) were measured. Genotype of MTNR1B gene single nucleotide polymorphism (rs10830963) was evaluated. In total, 44 patients (55%) had the genotype CC, 27 patients CG (33.8%) and 9 patients GG (11.2%). With the dietary intervention body mass index, weight, fat mass, systolic blood pressure, leptin levels and waist circumference decreased in both groups. There were no significant differences between gender groups on the reported effects in each genotype group. However, the improvement of anthropometric parameters was higher in subjects with CC genotype than (GC+GG) genotype. After dietary intervention and in males with CC genotype, insulin levels (-5.3±4.8UI/L vs 1.2±4.1UI/L; p<0.05) and HOMA-IR (-1.4±2.1 units vs 0.4±2.0 units; p<0.05) decreased. In the group of females with CC genotype, insulin levels (-3.5±2.1UI/L vs.-1.4±2.2UI/L: p<0.05) and HOMA-IR (-1.4±1.2 units vs.-0.1±1.3 units: p<0.05) decreased, too. However, these parameters remained unchanged in (GC+GG) group. Fasting glucose levels were higher in patients in (GC+GG). This study showed the association of rs10830963 MTNR1B single nucleotide polymorphism with body weight loss and changes in fasting insulin levels and HOMA-IR in obese subjects.

Metabolic effects of vitamin D supplementation in vitamin D deficient patients (a double-blind clinical trial)

BackgroundVitamin D has recently been given a lot of attention for its role in controlling insulin secretion. Many studies have spoken of its role in weight management, blood sugar control and many other metabolic variables. Patient and methodsIn a randomized double-blind clinical trial, 210 people with vitamin D deficiency were randomly allocated into two groups receiving vitamin D (50,000 units per week) or placebo for 8 weeks. ResultsVitamin D levels were significantly increased in the group receiving vitamin D supplementation (13.7±5.2 unit increase versus 0.8±2.8). The increased levels of vitamin D lead to significant changes in fasting insulin levels (6.8±8.1 unit reduction versus 2.3±3.7), a 2-h insulin (31.1±34.9 unit reduction versus 4.5±24.6) and Homeostasis Model Assessment (HOMA) indices. ConclusionCorrection of vitamin D deficiency leads to increased insulin sensitivity that was significantly able to maintain glucose in the normal range with lower levels of insulin.

The effects of short-term vitamin D supplementation on glucose metabolism in dialysis patients: a systematic review and meta-analysis.

We tested whether short-term vitamin D supplementation improves insulin resistance in patients with kidney disease, a condition with little intrinsic vitamin D activity. PubMed, EMBASE and CENTRAL were searched for relevant observational studies and randomized clinical trials (RCTs). Random-effects models were employed for meta-analysis, and effect sizes were summarized as standardized mean difference (SMD) with 95% confidence intervals. Separate analyses were done for RCTs and non-randomized intervention studies (NRIS). Seventeen studies (5 RCTs and 12 NRIS) were included. The meta-analysis population (n = 131) was mostly middle aged (40-50 years), male and non-diabetic, and on hemodialysis. The duration (4-12 weeks) and type of supplementation varied between studies. Among RCTs, compared to placebo, vitamin D supplementation was associated with significant decrease in fasting glucose [SMD -1.13, (-2.11 to -0.11)] and PTH levels [SMD -1.50, (-2.95 to -0.04)] but no difference in fasting insulin levels [SMD 1.32, (-0.15 to 2.79)]. Among NRIS, there was only a significant decrease in PTH levels [SMD -1.68, (-2.55 to -0.82)] between pre- and post-vitamin D treatment levels. Short-term (4-12 weeks) supplementation with vitamin D is associated with lower fasting glucose levels in ESRD with no change in fasting insulin levels. However, the findings from this study are limited by the studies that were used in the meta-analysis, which were mostly small, used multiple different vitamin D compounds and dosing regimens, and had large heterogeneity, and funnel plots showed that there was a dearth of studies with null or negative finding. Therefore, larger RCTs need to be performed to answer this important clinical question.

KCNJ11 E23K variant is associated with the therapeutic effect of sulphonylureas in Chinese type 2 diabetic patients.

The aim of the present study was to investigate the effect of the E23K variant of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene on gliclazide modified release (MR) treatment in newly diagnosed patients with type 2 diabetes mellitus (T2DM). A total of 108 diabetic patients with no history of antidiabetic medication was treated with gliclazide MR for 16weeks and underwent follow up at Weeks 2, 4, 8, 12 and 16. All patients were genotyped for KCNJ11 E23K (rs5219). At baseline, patients with the KK genotype had higher blood glucose and lower serum insulin levels after oral glucose administration than patients with the EE and EK genotypes (P<0.05 for all). During treatment, individuals with the KK genotype had lower fasting glucose levels and were more likely to attain the target fasting glucose level (Plog rank =0.028) than E allele carriers. Patients with the KK genotype had larger augmentations in changes (Δ) in acute insulin response (P=0.049) and Δ body mass index (P=0.003). Moreover, patients with the EK genotype had a lower variance in changes in fasting insulin levels (P=0.049) and homeostasis model assessment of β-cell function (P=0.021) than those with the KK genotype. The findings of the present study suggest that the KCNJ11 E23K variant is associated with a greater effect of sulphonylurea treatment in newly diagnosed Chinese patients with T2DM.

SOD1-G93A Mice Exhibit Muscle-Fiber-Type-Specific Decreases in Glucose Uptake in the Absence of Whole-Body Changes in Metabolism

Background: Skeletal muscles play an important role in systemic glucose homeostasis and are purported to be the origin of the altered metabolic state observed in amyotrophic lateral sclerosis (ALS). Objective: The purpose of this study was to evaluate whole-body and muscle-specific glucose metabolism in the SOD1-G93A mouse model of ALS. Methods: We assessed glucose tolerance in early-, middle-, and late-stage SOD1-G93A and control mice using an intraperitoneal glucose tolerance test. We then measured the respiratory exchange ratio (CO₂ production/O₂ consumption) as a function of fasting and feeding using indirect calorimetry in a subset of male mice at these time points. Finally, muscles from all mice were harvested to evaluate basal and insulin-stimulated glucose transport in fast- and slow-twitch muscles. Results: No changes in systemic glucose clearance were observed in SOD1-G93A mice at any stage, nor were there changes in fasting insulin levels. Indirect calorimetry revealed an increase in the respiratory exchange ratio during the fed state at middle, but not at early or late stages of disease. Middle-stage SOD1-G93A mice exhibited decreased insulin-stimulated glucose uptake in fast-twitch, but not slow-twitch, skeletal muscle. Late-stage SOD1-G93A mice exhibited decreased insulin-stimulated glucose uptake in both fast- and slow-twitch muscle, as well as increased basal (non-insulin-stimulated) glucose uptake. Conclusions: These results suggest that alterations in muscle metabolism occur in a fiber-type-specific manner in ALS, but do not necessarily lead to whole-body metabolic changes in SOD1-G93A mice.

Impact of hyperinsulinemia on the development of hypertension in normotensive, nondiabetic adults: a 4-year follow-up study

This study aimed to investigate the association between baseline fasting insulin levels, changes in fasting insulin levels, and future development of hypertension in normotensive, non-diabetic, healthy adults. We analyzed data from 11,123 adults, aged 20-65years, who had no history of hypertension or diabetes mellitus at a 2004 medical examination in a health promotion program and had attended a repeat examination in 2008. Subjects were divided into four groups according to baseline quartiles of fasting insulin and dichotomized fasting insulin levels at baseline and after 4years: low-low, low-high, high-low, high-high. We also assessed whether the association differed between the younger (20-40years) and older subjects (41-65years). In four years, 1142 subjects (10.3%) developed hypertension. The odds ratio (OR) for the development for hypertension increased as the quartiles of baseline fasting insulin levels and changes in fasting insulin levels increased from the first to the fourth quartile (OR 1.15, 1.35, and 1.95 vs. 1.07, 1.22, and 1.41, respectively), after adjusting for multiple factors. The OR for hypertension was 2.0-fold higher in the high-high group and 1.34-fold higher in the low-high group than in the low-low group. In comparing the results by age group, we found that these relationships were more prominent in younger subjects. High baseline and continuously increasing fasting insulin levels appeared to be independent determinants for the future development of hypertension during this 4-year follow-up study in normotensive, non-diabetic, healthy adults.

Comparison of the effects of simvastatin vs. rosuvastatin vs. simvastatin/ezetimibe on parameters of insulin resistance

Statin treatment may be associated with adverse effects on glucose metabolism. Whether this is a class effect is not known. In contrast, ezetimibe monotherapy may beneficially affect insulin sensitivity. The aim of this study was to compare the effects of three different regimens of equivalent low-density lipoprotein cholesterol (LDL-C) lowering capacity on glucose metabolism. A total of 153 patients (56 men), who had not achieved the LDL-C goal recommended by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) despite a 3-month dietary and lifestyle intervention, were randomly allocated to receive open-label simvastatin 40 mg or rosuvastatin 10 mg or simvastatin/ezetimibe 10/10 mg for 12 weeks. The primary end point was changes in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary endpoints consisted of changes in fasting insulin levels, fasting plasma glucose (FPG), glycosylated haemoglobin (HbA(1c) ), the HOMA of β-cell function (HOMA-B) (a marker of basal insulin secretion by pancreatic β-cells), LDL-C and high sensitivity C reactive protein (hsCRP). At week 12, all three treatment regimens were associated with significant increases in HOMA-IR and fasting insulin levels (p < 0.05 compared with baseline). No significant difference was observed between groups. No change in FPG, HbA(1c) and HOMA-B levels compared with baseline were noted in any of the three treatment groups. Changes in serum lipids and hsCRP were similar across groups. To the extent that simvastatin 40 mg, rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg are associated with adverse effects on insulin resistance, they appear to be of the same magnitude.

Responsiveness to metformin in girls with androgen excess: collective influence of genetic polymorphisms

To study the relationship between the responsiveness to metformin in girls with androgen excess and combinations of genetic variants-as reflected in a polymorphism score-in single nucleotide polymorphisms (OCT1, STK11, and FTO genes) and in the repeat numbers within the AR and SHBG genes. Longitudinal (1-year) follow-up. University hospital. Hyperandrogenic adolescent girls receiving metformin. Single nucleotide polymorphisms and repeat numbers were assessed in 104 adolescent girls with androgen excess. The polymorphism score was the sum of subscores given for response alleles in OCT1, STK11, and FTO and for high repeat numbers in SHBG and AR alleles. The response to metformin (850 mg/d) was judged by changes over 1 year in endocrine-metabolic state and body composition. Changes in fasting insulin levels, triacylglycerol levels, LDL-HDL ratio, and body composition differed strikingly by polymorphism score. Collectively, genetic polymorphisms had a major influence on the responsiveness to metformin in adolescent girls with androgen excess.

Alteration of insulin sensitivity by sex hormones during the menstrual cycle.

It is well established that insulin resistance and impaired insulin secretion are two major prerequisites in the development of type 2 diabetes. Given the growing global epidemic of obesity, it is expected that the number of people with insulin resistance will expand exponentially. To maintain glucose homeostasis, insulin action, reflected by insulin sensitivity measured in vivo, is regulated by a well organized, but complicated, hierarchical mechanism. In this regard, many studies have shown that environmental factors might have a great influence on insulin sensitivity and these issues are further complicated when interaction between genes and the environment is taken into consideration1. Additionally, a number of studies have shown that the degree of insulin sensitivity is also influenced by many biological factors, in particular, hormone alterations, which might account for the diurnal changes of insulin sensitivity in normal and diabetic individuals or involve the occurrence of the dawn phenomenon. Extensive studies were carried out to determine how sex hormones harness insulin sensitivity or predispose humans to the development of diabetes2. In a recent article, obtained from The BioCycle Study, Yeung et al.3 reported that, in a group of relatively healthy premenopausal women, insulin resistance, expressed by homeostasis model assessment for insulin resistance (HOMA‐IR), changed slightly, but significantly, during the normal menstrual cycle. Specifically, HOMA‐IR rose from 1.35 in the midfollicular phase to 1.59 (with a magnitude of increase of 17.8%) during the early luteal phase and decreased to 1.55 (by 14.8%) in the late luteal phase. These changes were positively associated with levels of estradiol and progesterone, but negatively associated with follicle stimulating hormone (FSH) and sex hormone binding globin (SHBG). In addition to findings from previous studies showing the impact of menstrual cycle variability on insulin sensitivity, this BioCycle Study enrolled the greatest number of healthy women (n = 257) and had the most frequent visits (eight visits during a cycle period), designed to monitor women at peak fertility. Thus, the findings from this study, which has overcome the shortages of previous inconsistent reports, should be reliable. However, concerns were raised as to how accurate HOMA‐IR is in capturing the degree of insulin resistance4. It will be of great value, although difficult, to use more precise measures of insulin resistance, such as the glucose clamp study, in those studied participants. The physiological effects of circulating estradiol and progesterone levels on insulin resistance in premenopausal women might be distinct from pharmacological applications in postmenopausal women. The present author and others have shown that oral contraceptive pills might decrease insulin resistance and increase cardiovascular risk in young women, whereas transdermal use of estrogen might prevent these untoward effects5. It is postulated that estrogen‐induced increases in glucocorticoid activity might account for these unwanted effects. In addition, the influence of long‐term use of estrogen might be different from that of short‐term use, with the former preserving insulin secretion and maintaining glucose homeostasis. In this article, the finding that alterations of HOMA‐IR primarily reflected changes in fasting insulin levels and not fasting glucose levels3 is not unexpected, given the tight regulation of insulin secretion during alterations of insulin sensitivity in healthy individuals. One of the limitations of the study by Yeung et al.3 was the lack of measurement of testosterone, which was reported to be associated with insulin resistance, although the use of SHBG in this study might partially reflect the bioavailability and action of testosterone. In addition, the association between HOMA‐IR and SHBG became insignificant after adjustment of body mass index (BMI), showing that these associations might be mediated through adiposity in the studied population. Finally, although the alterations of insulin resistance during the menstrual cycle might be considered as minor, caution should be taken when recruiting premenopausal women to serve as study volunteers, especially when comparing changes of insulin resistance before and after certain interventional trials.

Hyperinsulinemia and the Development of Nonalcoholic Fatty Liver Disease in Nondiabetic Adults

Background Insulin resistance is known to be the most important pathogenic factor in the development of nonalcoholic fatty liver disease. We performed a prospective study to analyze the associations of baseline and changes in fasting insulin levels with future development of nonalcoholic fatty liver disease in nondiabetic adults over a 5-year period. Methods This study was performed in 4954 subjects who did not have diabetes or nonalcoholic fatty liver disease and who participated in a health checkup program in both 2003 and 2008. The presence of nonalcoholic fatty liver disease was defined by ultrasonographic examination. Subjects were divided into 4 groups according to the baseline quartiles of fasting insulin and dichotomized fasting insulin levels at baseline and after 5 years: low-low, low-high, high-low, high-high. Results After 5 years, 644 subjects (13%) developed nonalcoholic fatty liver disease. The odds ratio (OR) for development of nonalcoholic fatty liver disease increased as the quartiles of the baseline fasting insulin levels increased from the first to the fourth quartile (1.00 vs. 0.99, 1.44, 1.65, respectively). The OR for nonalcoholic fatty liver disease was 2.5-fold higher in the high-high group and 1.6-fold higher in the low-high group compared with that of the low-low group. The OR for nonalcoholic fatty liver disease increased as the quartile of changes in fasting insulin level over the 5-year period increased. Conclusion High baseline and continuously increasing fasting insulin levels were the independent determinants for future development of nonalcoholic fatty liver disease during a 5-year follow-up in nondiabetic healthy adults.