Insulin Sensitivity Index Research Articles

The Effects of C. lacerata on Insulin Resistance in Type 2 Diabetes Patients.

Background Several experimental studies have suggested beneficial effects of Ceriporia lacerata on glucose metabolism. However, there has been no human study assessing the effects of C. lacerata on glucose metabolism. Therefore, we investigated whether C. lacerata improves glucose control and insulin resistance in type 2 diabetes patients. Methods Ninety patients diagnosed with type 2 diabetes (T2DM) for more than 6 months were enrolled. Subjects were randomly divided into placebo (n = 45) or C. lacerata (n = 45) groups and then assigned to take placebo or C. lacerata capsules (500 mg/capsule) for a 12-week intervention period. Biochemical markers, including fasting glucose, 2-hour postprandial plasma glucose, and lipid profile levels, as well as insulin, c-peptide, and Hba1c, were measured. Furthermore, insulin sensitivity indices, such as HOMA-IR, HOMA-beta, and QUICKI, were assessed before and after the 12-week administration. Results Eighty-four patients completed the study. There were no significant differences in fasting, postprandial glucose, HbA1c, or lipid parameters. HOMA-IR and QUICKI indices were improved at week 12 in the C. lacerata group, especially in subjects with HOMA-IR of 1.8 or more (p < 0.05). Fasting, postprandial c-peptide, and insulin levels decreased at week 12 in the C. lacerata group (p < 0.05). These significant differences were not observed in the placebo group. Conclusion Twelve-week administration of C. lacerata in T2DM patients resulted in significant improvement in insulin resistance, especially in those with lower insulin sensitivity. A larger population study with a longer follow-up period and an effort to elucidate the mechanism is warranted to further assess the effects of C. lacerata on T2DM patients.

Is Methylprednisolone Acetate-Related Insulin Resistance Preventable in Cats?

Methylprednisolone acetate (MPA) is often prescribed to cats despite being recognized eventually as diabetogenic. To assess MPA-related insulin resistance and evaluate the efficacy of metformin or an obesity and diabetes mellitus (O&D) adjuvant diet as protective factors, a randomized clinical trial was conducted with 28 owned cats undergoing glucocorticoid therapy. A single MPA dose of 20 mg intramuscularly was administered to each cat. Controls (n = 10) received only MPA. In the diet group (n = 9), replacement of their habitual diet by ad-libitum feeding of a feline commercial O&D diet (Equilíbrio O&D, Total Alimentos ADM) was made. In the metformin group (n = 9), metformin chlorhydrate 25mg/cat PO/q24h was administered for 30 days. All patients were clinically evaluated at baseline (T0), day 15 (T15), and day 30 (T30) and blood draw for complete blood count, serum biochemistry, and determination of insulin concentrations. Fasting Insulin Sensitivity Index (SI), Amended Insulin to Glucose Ratio (AIGR), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and Homeostatic Model Assessment of beta-cell function (HOMA-B) were calculated based on fasting glycemia and insulinemia. All groups showed significantly higher levels (P < .05) of neutrophils, albumin, glucose, cholesterol, triglycerides, and serum insulin at T15. Patients in the metformin group showed also higher SI, AIGR, and HOMA-IR results at T15. Also, at T15, reduced levels (P < .05) of eosinophils, lymphocytes, and creatinine were documented in all groups. An MPA single dose induced changes in insulin sensitivity in cats; however, neither metformin nor O&D feeding used in this study was effective as protective factors against MPA-related insulin resistance.

Pre-pregnancy BMI but not mild stress directly influences Interleukin-6 levels and insulin sensitivity during late pregnancy.

This study investigates the influence of maternal stress during pregnancy on maternal insulin sensitivity and Interleukin-6 (IL-6) levels in pregnant women (N = 277) in dependence of pre-pregnancy Body-Mass-Index (BMI). Gestational diabetes was diagnosed in 80 women. We used the Patient Health Questionnaire (PHQ-D) to investigate maternal stress during pregnancy with a higher scoring indicating higher maternal stress level. IL-6 and cortisol were measured and maternal insulin sensitivity was assessed with the non-esterified fatty acid insulin sensitivity index (NEFA-ISI). Generalized Linear Model analysis was used to analyze effects within different stress groups. Maternal low stress symptoms during pregnancy showed no significant association with maternal insulin sensitivity or IL-6. Higher cortisol levels during pregnancy were associated with elevated IL-6 concentrations. Pre-pregnancy BMI had the strongest positive effect on IL-6 levels and was negatively associated with insulin sensitivity during pregnancy. Therefore, preconceptional interventions to reduce BMI are needed to improve maternal metabolism during pregnancy.

Preventive Impact of Long-Term Ingestion of Chestnut Honey on Glucose Disorders and Neurodegeneration in Obese Mice.

The purpose of the present study was to evaluate the impact of long-term honey ingestion on metabolic disorders and neurodegeneration in mice fed a high-fat diet (HFD). Three groups of mice were fed with a standard diet (STD), HFD or HFD supplemented with honey (HFD-H) for 16 weeks. Biochemical, histological, Western blotting, RT-PCR and Profiler PCR array were performed to assess metabolic parameters, peripheral and central insulin resistance and neurodegeneration. Daily honey intake prevented the HFD-induced glucose dysmetabolism. In fact, it reduced plasma fasting glucose, insulin and leptin concentrations and increased adiponectin levels. It improved glucose tolerance, insulin sensitivity and HOMA index without affecting plasma lipid concentration. HFD mice showed a significantly higher number of apoptotic nuclei in the superficial and deep cerebral cortex, upregulation of Fas-L, Bim and P27 (neuronal pro-apoptotic markers) and downregulation of Bcl-2 and BDNF (anti-apoptotic factors) in comparison with STD- and HFD-H mice, providing evidence for honey neuroprotective effects. PCR-array analysis showed that long-term honey intake increased the expression of genes involved in insulin sensitivity and decreased genes involved in neuroinflammation or lipogenesis, suggesting improvement of central insulin resistance. The expressions of p-AKT and p-GSK3 in HFD-H mice, which were decreased and increased, respectively, in HFD mouse brain, index of central insulin resistance, were similar to STD animals supporting the ability of regular honey intake to protect brain neurons from insulin resistance. In conclusion, the present results provide evidence for the beneficial preventative impact of regular honey ingestion on neuronal damage caused by HFD.

Hematologic malignancies magnify the effect of body mass index on insulin resistance in cancer survivors

AbstractCancer survivors are at increased risk of type 2 diabetes, which usually develops from obesity and insulin resistance. Whether diabetes susceptibility is due to shared risk factors for cancer and insulin resistance or directly related to cancer and its treatment is unknown. We investigated effect modification between malignancy and body mass index (BMI) as determinants of insulin sensitivity in patients with hematologic malignancies and controls without cancer. In a cross-sectional study of 43 individuals without diabetes (20 patients with treated hematologic malignancies; 23 controls without malignancies), we measured insulin-stimulated whole-body glucose use (M) by hyperinsulinemic euglycemic clamp. Insulin sensitivity index (ISI) was calculated by dividing M over steady-state plasma insulin. Inflammatory cytokines were measured in plasma. Controls were more obese and included more non-White individuals and women vs patients with hematologic malignancies. Patients with cancer exhibited greater insulin sensitivity (median ISI, 42.4 mg/kg/min/[μU/mL]; interquartile range [IQR], 33.9-67.2 vs 23.4 mg/kg/min/[μU/mL]; IQR, 12.9-29.2; P < .001) and higher interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) concentrations vs controls. Patients with cancer demonstrated greater reduction in ISI with increasing BMI vs controls, which remained significant after adjustment for sex and race (β = −2.6 units; 95% confidence interval, −4.8 to −0.4; P interaction = .024). This interaction also remained significant after adjusting for log IL-6 (P interaction = .048) and log MCP-1 (P interaction = .021). Cancer survivors had disproportionately greater insulin resistance with increasing BMI vs controls without malignancies. Effect modification between cancer and BMI in determining insulin sensitivity implicated cancer-specific etiologies in glucose dysregulation and could partially explain excess diabetes diagnoses among oncology patients.

Combination therapy with pioglitazone/exenatide/metformin reduces the prevalence of hepatic fibrosis and steatosis: The efficacy and durability of initial combination therapy for type 2 diabetes (EDICT).

To compare the efficacy of triple therapy (metformin/exenatide/pioglitazone) versus stepwise conventional therapy (metformin → glipizide → glargine insulin) on liver fat content and hepatic fibrosis in newly diagnosed, drug-naïve patients with type 2 diabetes. Sixty-eight patients completed the 6-year follow-up and had an end-of-study (EOS) FibroScan to provide measures of steatosis (controlled attenuation parameter [CAP] in dB/m) and fibrosis (liver stiffness measurement [LSM] in kPa); 59 had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to measure liver fat. At EOS, HbA1c was 6.8% and 6.0% in triple and conventional therapy groups, respectively (P=.0006). Twenty-seven of 39 subjects (69%) receiving conventional therapy had grade 2/3 steatosis (CAP, FibroScan) versus nine of 29 (31%) in triple therapy (P=.0003). Ten of 39 (26%) subjects receiving conventional therapy had stage 3/4 fibrosis (LSM) versus two of 29 (7%) in triple therapy (P=.04). Conventional therapy subjects had more liver fat (MRI-PDFF) than triple therapy (12.9% vs. 8.8%, P=.03). The severity of steatosis (CAP) (r=0.42, P < .001) and fibrosis (LSM) (r=-0.48, P < .001) correlated inversely with the Matsuda Index of insulin sensitivity, but not with percentage body fat. Aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), plasma AST, and alanine aminotransferase (ALT) all decreased significantly with triple therapy, but only the decrease in plasma AST and ALT correlated with the severity of steatosis and fibrosis at EOS. At EOS, subjects with type 2 diabetes treated with triple therapy had less hepatic steatosis and fibrosis versus conventional therapy; the severity of hepatic steatosis and fibrosis were both strongly and inversely correlated with insulin resistance; and changes in liver fibrosis scores (APRI, NFS, Fibrosis-4, and AST/ALT ratio) have limited value in predicting response to therapy.

Spinal cord-wide structural disruption in type 2 diabetes rescued by exenatide "a glucagon-like peptide-1 analogue" via down-regulating inflammatory, oxidative stress and apoptotic signaling pathways

The mechanisms of spinal cord-wide structural and functional disruption in diabetic patients remain elusive. This study evaluated histopathological alterations of the spinal cord cytoarchitecture in T2DM model of rats and assessed the potential ameliorating effect of exenatide "a potent GLP-1 analogue". Thirty male rats were allocated into three groups; I (control), II (Diabetic): T2DM was induced by high fat diet for 8 weeks followed by a single I.P injection of STZ (25 mg/kg BW) and III (Diabetic/Exenatide): T2DM rats injected with exenatide (10 μg/Kg, S.C. twice daily for 2 weeks). Neurobehavioral sensory and motor tests were carried out and glycemic control biomarkers and indices of insulin resistance and sensitivity were measured. In addition, the spinal cord was processed for histological and immunohistochemical studies besides assessing its tissue homogenate levels of pro-inflammatory/anti-inflamatory cytokines and oxidant/antioxidant biomarkers. Moreover, RT-qPCR was performed to measure the expression of proapoptotic/antiapoptotic and neurotrophic genes. The diabetic rats exhibited thermal hyperalgesia, mechanical allodynia and decreased locomotor activity along with increased serum glucose, insulin, HbA1c, HOMA-IR while, quantitative insulin sensitivity check index (QUICKI) was decreased. Also, IL-1β NF-kB, MDA increased while IL-10, SOD activity and β-endorphin decreased in the spinal tissue. Up regulation of caspase-3 and down regulation of Bcl-2, nerve growth factor (NGF) and glial cell-derived neurotrophic (GDNF) in diabetic rats. Also, they exhibited histopathological changes and increased CD68 positive microglia and Bax immunoreactivity in the spinal cord. Subsequent to exenatide treatment, most biomolecular, structural and functional impairments of the spinal cord were restored in the diabetic rats. In conclusion, the neuro-modulating effect of exenatide against diabetic-induced spinal cord affection warrants the concern about its therapeutic relevance in confronting the devastating diabetic neuropathic complications.

Pancreatic cancer-associated diabetes mellitus is characterized by reduced β-cell secretory capacity, rather than insulin resistance

AimsThe early distinction of pancreatic cancer associated diabetes (PaCDM) in patients with elderly diabetes is critical. However, PaCDM and type 2 diabetes mellitus (T2DM) remain indistinguishable. We aim to address the differences between the pancreatic and gut endocrine hormones of patients with PaCDM and T2DM. MethodsA total of 44 participants underwent mixed meal tolerance test (MMTT). Fasting and postprandial concentrations of insulin, C-peptide, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and gastric inhibitory peptide (GIP) were measured. Insulin sensitivity and secretion indices were calculated. One-way ANOVA with post-hoc analysis was used for statistical analysis. ResultsInsulin and C-peptide responses to MMTT were blunted in PaCDM patients compared with T2DM. Baseline concentrations and AUCs differed. PaCDM patients showed lower insulin secretion capacity but better insulin sensitivity than T2DM patients. The peak concentration and AUC of PP in T2DM group were higher than healthy controls, but in accordance with PaCDM. PaCDM patients presented lower baseline GLP-1 concentration than T2DM patients. No between-group differences were found for glucagon and GIP. ConclusionsPaCDM patients had a lower baseline and postprandial insulin and C-peptide secretion than T2DM patients. Reduced insulin secretion and improved peripheral sensitivity were found in PaCDM patients compared with T2DM.

Sex-Specific Aspects of Skeletal Muscle Metabolism in the Clinical Context of Intensive Care Unit-Acquired Weakness.

(1) Background: Female sex is considered a risk factor for Intensive Care Unit-Acquired Weakness (ICUAW). The aim is to investigate sex-specific aspects of skeletal muscle metabolism in the context of ICUAW. (2) Methods: This is a sex-specific sub-analysis from two prospectively conducted trials examining skeletal muscle metabolism and advanced muscle activating measures in critical illness. Muscle strength was assessed by Medical Research Council Score. The insulin sensitivity index was analyzed by hyperinsulinemic-euglycemic (HE) clamp. Muscular metabolites were studied by microdialysis. M. vastus lateralis biopsies were taken. The molecular analysis included protein degradation pathways. Morphology was assessed by myocyte cross-sectional area (MCSA). Multivariable linear regression models for the effect of sex on outcome parameters were performed. (3) Results: n = 83 (♂n = 57, 68.7%; ♀n = 26, 31.3%) ICU patients were included. ICUAW was present in 81.1%♂ and in 82.4%♀ at first awakening (p = 0.911) and in 59.5%♂ and in 70.6%♀ at ICU discharge (p = 0.432). Insulin sensitivity index was reduced more in women than in men (p = 0.026). Sex was significantly associated with insulin sensitivity index and MCSA of Type IIa fibers in the adjusted regression models. (4) Conclusion: This hypothesis-generating analysis suggests that more pronounced impairments in insulin sensitivity and lower MCSA of Type IIa fibers in critically ill women may be relevant for sex differences in ICUAW.

The sodium\u2013glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes

Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction.

Lowering of Blood Glucose Levels with the Peptide Mixture Deglusterol in In Vitro and In Vivo Models.

This study aimed to investigate the blood glucose-lowering effect of the peptide complex Deglusterol, which was isolated from corn extract, in insulin-resistance models. It was found to inhibit insulin receptor substrate (IRS) Ser302 phosphorylation, known as the insulin resistance mechanism, through the inhibition of tumor necrosis factor-α (TNF-α) signaling and the induction of AMP-activated protein kinase phosphorylation. Furthermore, the phosphorylation of IRS Tyr632, phosphoinositide 3-kinase (PI3K), and AKT that is involved in the insulin action mechanism was decreased by TNF-α, whereas Deglusterol increased their phosphorylations, leading to an increase of glucose uptake rate by 190% through glucose transporter type 4 (GLUT4) compared with TNF-α-treated group in C2C12 cells. In addition to insulin signaling activation, Deglusterol treatment resulted in significantly greater mRNA expressions of IRS (190%) and GLUT4 (140%) as well as that of leptin (260%) and adiponectin (140%), which are indicators of insulin sensitivity. In animal models with type 2 diabetes, the blood glucose concentrations in the Deglusterol-administered group were significantly reduced by 50% compared with the control group. Deglusterol suppressed insulin resistance and restored insulin sensitivity, which contributed to lowering blood glucose concentrations in the insulin-resistant models, suggesting its potential as a blood glucose-lowering agent for people at high risk of type 2 diabetes or prediabetes.

Treatment of acromegaly has substantial effects on body composition: a long-term follow-up study.

Acromegaly is associated with changes in body composition. Long-term changes following acromegaly treatment and the impact of different treatments have been less investigated. We performed a retrospective study in 201 patients with acromegaly. Body composition was assessed by dual-energy X-ray absorptiometry. To investigate the specific effects of treatment vs aging, changes in body composition were compared in one group of patients evaluated both at the time of active and controlled disease (active-to-controlled (A>C); n = 31) and in another group of patients evaluated two times while the disease was controlled (controlled-to-controlled (C>C); n = 32). In the whole cohort, insulin-like growth factor I (IGF-I) was correlated with fat (r = -0.369; P < 0.001) and lean mass (r = 0.383; P < 0.001). Patients from A>C and C>C groups were comparable for age, sex, BMI and follow-up duration (P = n.s.). Reduction in IGF-I levels was associated with an increase in fat mass and a decrease in lean mass in the A>C group, which was four and eight times more pronounced compared to the C>C group (fat mass: +39 ± 34% vs +10 ± 15%, P < 0.001; lean mass: -8 ± 8% vs -0.2 ± 6%, P < 0.001, respectively). Changes in fat mass were negatively associated with IGF-I (r = -0.450; P = 0.011) and independent of the individual therapy. The daily dose of pegvisomant correlated with fat mass (r = 0.421; P = 0.002) and insulin sensitivity index (r = -0.466; P < 0.001). Treatment of acromegaly strongly impacts body composition until biochemical disease remission, characterized by an increase in fat mass and a decrease in lean mass. These changes are closely associated with the normalization of IGF-I. Thereafter, body composition changes are similar to what is observed with aging.

Effect of Nano-Oleanolic Acid Combined With Lipid-Lowering Ketones on Insulin Resistance in Rats with Gestational Diabetes.

Diabetes is a widespread metabolic syndrome, an important complication during pregnancy. Most cases are type 2 diabetes, which has attracted the attention of the World Health Organization. The typical feature of T2DM is insulin resistance (IR). Its mechanism remains unclear, but it mainly manifests through parameters like insulin sensitivity, blood glucose level, and liver stability. Oxidative stress and insulin transduction play an important role in IR. This study simulates the disease situation, establishes a high-fat and high-fructose-induced model induced by tert-butyl hydroperoxide (tBHP), and adopts nano-sized oleanolic acid combined with lipid-lowering ketones to explore improvement in the IR mechanism. We found combining nano-sized oleanolic acid and lipid-lowering ketones can slow down the weight gain process in rats, reduce fasting blood glucose levels, increase the insulin sensitivity index, reduce the serum MDA, NO, and triglyceride content, and increase SOD, CAT activity. In summary, our results show that the combined use of nano-sized oleanolic acid and lipid-lowering ketone in pregnant rats with double height can reduce glucose metabolism, delay lipid production, and reduce oxidative stress, which is useful for further treatment and interpretation of T2DM The mechanism provides a theoretical basis.

Preventive effects of polysaccharides from Physalis alkekengi L. on dietary advanced glycation end product-induced insulin resistance in mice associated with the modulation of gut microbiota

Advanced glycation end products (AGEs) are commonly found in thermally processed foods, and long-term high AGE feeding has been reported to have negative effects on body health. In the current study, the effect of Physalis alkekengi L. fruit polysaccharide (PFP) on preventing dietary AGE-induced insulin resistance (IR) in mice was investigated. The results showed that PFP administration can significantly ameliorate hyperglycemia, dyslipidemia, and insulin resistance induced by dietary AGEs in mice. Compared to AGE-treated mice, the homeostasis model assessment for insulin resistance (HOMA-IR) index and insulin sensitivity (HOMA-IS) index of PFP-treated mice were improved significantly (p < 0.05). The levels of endotoxin and inflammatory cytokines in the liver decreased, while the levels of insulin receptor substrate-1 and insulin receptor substrate-2 in the liver increased (p < 0.05). The 16S rRNA analysis showed that PFP administration reversed the Bacteroidetes/Firmicutes ratio and reduced lipopolysaccharide generation and inflammation-related bacteria, including Desulfovibrio and Acetatifactor. In addition, PFP administration also increased short-chain fatty acid levels in feces compared to dietary AGE-treated mice. Spearman's correlation analysis showed that certain specific genera, including Alistipes and Caproiciproducens, are closely related to IR-related parameters. These findings suggest that PFP can prevent dietary AGE-induced IR by modulating the gut microbiota and increasing microbial metabolites.

Association of thyroid function with insulin resistance: data from two population-based studies.

ObjectiveThyroid dysfunction is associated with relevant disturbances in glucose metabolism. Moreover, thyroid function undergoes important changes with ageing. The objective of this study was to investigate the association of thyroid function with insulin resistance with particular consideration of possible age-related effect modifications.DesignA sample of 4193 participants from two independent epidemiological studies, the Study of Health in Pomerania-TREND-0 and the Berlin Aging Study II, was included in this cross-sectional analysis.MethodsInsulin resistance was estimated by homeostasis model of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI). Associations of thyroid biomarkers (thyroid-stimulating hormone, free thyroxine, and free triiodothyronine (fT3)) with parameters of glucose metabolism were analysed by regression models adjusted for age, sex, smoking status, and study site.ResultsA higher fT3 was significantly associated with higher fasting glucose and higher fasting and 2-h postload insulin levels, a higher HOMA-IR, and lower ISI. A higher fT3 was also associated with a higher risk for impaired fasting glucose (RR 1.09, 95 CI 1.02; 1.18; P = 0.017). Many of these associations between thyroid markers and parameters of glucose metabolism were significant in young and middle-aged participants but not in older individuals.ConclusionsThe main finding of this study was a consistent association of fT3 with almost all markers of insulin resistance. However, this effect seems to be wearing off in higher age highlighting a potential age-related modification of the interaction between thyroid function and glucose metabolism. Further studies are needed to clarify causal relationships.

Impact of protocol-based physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients.

BackgroundThe impact of physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients is not well understood.MethodsThis pooled analysis investigates the impact of different physiotherapeutic strategies on insulin sensitivity in critically ill patients. We pooled data from two previous trials in adult patients with sequential organ failure assessment score (SOFA)≥ 9 within 72 h of intensive care unit (ICU) admission, who received hyperinsulinaemic euglycaemic (HE) clamps. Patients were divided into three groups: standard physiotherapy (sPT, n = 22), protocol‐based physiotherapy (pPT, n = 8), and pPT with added muscle activating measures (pPT+, n = 20). Insulin sensitivity index (ISI) was determined by HE clamp. Muscle metabolites lactate, pyruvate, and glycerol were measured in the M. vastus lateralis via microdialysis during the HE clamp. Histochemical visualization of glucose transporter‐4 (GLUT4) translocation was performed in surgically extracted muscle biopsies. All data are reported as median (25th/75th percentile) (trial registry: ISRCTN77569430 and ISRCTN19392591/ethics approval: Charité‐EA2/061/06 and Charité‐EA2/041/10).ResultsFifty critically ill patients (admission SOFA 13) showed markedly decreased ISIs on Day 17 (interquartile range) 0.029 (0.022/0.048) (mg/min/kg)/(mU/L) compared with healthy controls 0.103 (0.087/0.111), P < 0.001. ISI correlated with muscle strength measured by medical research council (MRC) score at first awakening (r = 0.383, P = 0.026) and at ICU discharge (r = 0.503, P = 0.002). Different physiotherapeutic strategies showed no effect on the ISI [sPT 0.029 (0.019/0.053) (mg/min/kg)/(mU/L) vs. pPT 0.026 (0.023/0.041) (mg/min/kg)/(mU/L) vs. pPT+ 0.029 (0.023/0.042) (mg/min/kg)/(mU/L); P = 0.919]. Regardless of the physiotherapeutic strategy metabolic flexibility was reduced. Relative change of lactate/pyruvate ratio during HE clamp is as follows: sPT 0.09 (−0.13/0.27) vs. pPT 0.07 (−0.16/0.31) vs. pPT+ −0.06 (−0.19/0.16), P = 0.729, and relative change of glycerol concentration: sPT −0.39 (−0.8/−0.12) vs. pPT −0.21 (−0.33/0.07) vs. pPT+ −0.21 (−0.44/−0.03), P = 0.257. The majority of ICU patients showed abnormal localization of GLUT4 with membranous GLUT4 distribution in 37.5% (3 of 8) of ICU patients receiving sPT, in 42.9% (3 of 7) of ICU patients receiving pPT, and in 53.8% (7 of 13) of ICU patients receiving pPT+ (no statistical testing possible).ConclusionsOur data suggest that a higher duration of muscle activating measures had no impact on insulin sensitivity or metabolic flexibility in critically ill patients with sepsis‐related multiple organ failure.

Marine Oil from C. finmarchicus Enhances Glucose Homeostasis and Liver Insulin Resistance in Obese Prediabetic Individuals.

The intermediate state between normal glucose tolerance and overt type 2 diabetes mellitus is associated with micro- and macrovascular diseases, requiring safe and cost-effective treatment measures interventions. A novel source of LC n-3 FAs is Calanus finmarchicus Oil, which showed promising effects on glucose homeostasis in preclinical studies due to anti-obesity effects and/or anti-inflammatory properties. In total, 43 obese patients (BMI: 31.7 ± 5.2 kg/m2) were allocated in the following two groups: (1) Calanus oil group (2 g CO/day) and (2) placebo group (2 g paraffin oil/day). Markers of glucose metabolism, body composition and energy intake were measured at the beginning (t0), after 12 weeks (t12) and 16 weeks (t16). Overall, parameters reflecting abnormal glucose homeostasis and insulin resistance in the liver, including fasting insulin (−2.9 mU/L ± 4.10, p < 0.05), HOMA-IR (−0.9 ± 1.28, p < 0.05) and hepatic insulin resistance index (−1.06 ± 1.72 × 106, p < 0.05) significantly enhanced after a 12-week CO-intervention, while no differences were observed in HbA1c, AUC0–2h Glucose, AUC0–2h Insulin, 2 h plasma glucose and muscle insulin sensitivity index. Our results indicate that Calanus oil causes beneficial effects on glucose metabolism and insulin resistance in obese patients, with clinical relevance to be verified in further studies. In addition, the possible active compounds and their mechanisms of action should be elucidated.

The effect of visfatin genotype on insulin pump therapy on quality of life in patients with type I diabetes.

Diabetes is associated with an increase in other chronic diseases and an increase in mortality. The individual differences influence the treatment of this disease in pharmacokinetics and clinical responses. One of the important factors related to individual differences includes genetic factors in transmission, metabolism, and drug function. On the other hand, this disease has a significant impact on the patients' quality of life and their family. Therefore, this study aimed to investigate the role of single nucleotide polymorphism (rs2110385) of the visfatin gene on insulin required to maintain glucose homeostasis and to evaluate the effect of insulin pump therapy on the quality of life in type 1 diabetic patients. In this regard, this study was performed on 47 patients with type 1 diabetes. The short form of the Diabetes Quality of Life Questionnaire (DQOL) was used to record information. Laboratory tests also included FBS, HbA1C, G2h, serum levels of visfatin, insulin, and adiponectin. Insulin resistance (HOMA) and insulin sensitivity (QUICKI) indices were calculated. The polymorphism of the studied genotype was performed by the PCR-RFLP method. The results showed that the scores of both dimensions of quality of life, including patient care behaviors and satisfaction with the disease control after the intervention increased significantly (P <0.001). There was a significant and direct relationship between the patient's age and the duration of the disease with the score of increasing patients' quality of life. No significant differences were found between HbA1C, G2h, FBS levels, fasting insulin concentration, HOMA, and QUICKI indices. The insulin dose used to maintain glucose homeostasis at the same levels was significantly lower in the GG genotype than in other genotypes. In general, the present study results showed that insulin pump therapy and its dimensions could improve the life quality of patients with type 1 diabetes. Also, genetic evaluation of individuals helps to provide the correct and accurate dose of insulin with the help of the insulin pump for these patients to increase their quality of life as much as possible.

Clinical Efficacy Evaluation and Long-Term Prognosis of Glucagon-Like Peptide-1 Combined with Sodium Glucose Cotransporter-2 Inhibitor in Diabetes

To investigate the clinical worth of glucagon-like peptide-1 receptor agonist (liraglutide) combined with sodium glucose cotransporter-2 inhibitor (dapagliflozin) in the treatment of overweight or obesity patients with type 2 diabetes mellitus and to explore whether the beneficial effect of the combination can persist during a 1 y follow-up. Eighty overweight or obesity type 2 diabetes mellitus patients admitted to a hospital from January 2019 to January 2020 were randomly divided into a control group and an observation group, with 40 cases in each group. The control group was treated with liraglutide and the experimental group was treated with basic dapagliflozin in the control group. All patients were continuously treated for 12 w. The measurement results of parameters before and after treatment, the changes in glucose metabolism parameters, blood lipid metabolism parameters and the occurrence of adverse reactions during treatment were recorded. After that, 74 treated patients were followed up for 1 y (6 refused) and measurements of various parameters were recorded. The differences in body mass index, waist circumference, hemoglobin A1c, fasting plasma glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, lowdensity lipoprotein cholesterol, homeostatic model assessment-insulin resistance, homeostatic model assessment-beta and insulin sensitivity index before and after treatment in the experimental group were higher than those in the control group (p<0.05). Weight loss during treatment was sustained over 1 y in both groups, with more significant changes in the experimental group. The combination of glucagon-like peptide-1 agonist and sodium glucose cotransporter-2 inhibitor can improve diabetes in overweight or obesity patients with type 2 diabetes mellitus and effectively reduce blood glucose and body mass index, which is of great significance for reducing body weight and improving efficacy. Therefore, using glucagonlike peptide-1 agonists and sodium glucose cotransporter-2 inhibitors in overweight, diabetic patients is a promising option.

Correlations between glycosylated hemoglobin and glucose levels in Chinese older adults with newly diagnosed type 2 diabetes mellitus.

To explore the correlations between glycosylated hemoglobin (HbA1c) and glucose levels in older adults with newly diagnosed type 2 diabetes mellitus (T2DM). A total of 783 participants aged ≥60 years were enrolled. The 75-g oral glucose tolerance test (OGTT) was conducted and HbA1c was measured. The participants were divided into normal glucose tolerance (NGT)HbA1c, Pre-DMHbA1c, and T2DMHbA1c groups based on the HbA1c diagnostic criteria. The correlations between HbA1c and glucose levels of the OGTT were analyzed. When HbA1c ≥ 6.5% in older people, HbA1c was positively correlated with Glucose 0 min and 120 min of the OGTT (r = 0.335, 0.247; all p < 0.05, respectively). When HbA1c was between 5.7% and 6.4%, HbA1c was positively correlated with Glucose 0 min and 120 min (r = 0.298, 0.474; all p < 0.01, respectively). When HbA1c ≤ 5.6%, HbA1c was positively correlated with Glucose 0 min and 120 min (r = 0.301, 0.357; all p < 0.01, respectively). HbA1c was positively correlated with HOMA-IR (r = 0.368, p < 0.01), while it was negatively correlated with HOMA-β, ΔI30/ΔG30, IG120, and GDI(r = -0.267, -0.397,-0.364,-0.397; all p < 0.01, respectively). After adjustment for confounders, the correlations of HbA1c with Glucose 0 min and 120 min, insulin sensitivity and β-cell function indexes still existed. When HbA1c ≥ 6.5%, there were 93.3% T2DMOGTT and 6.7% Pre-DMOGTT subjects. When HbA1c < 6.5%, there were 17.7% T2DMOGTT, 39.5% Pre-DMOGTT (including 2.5% IFGOGTT, 36.1% IGTOGTT and 0.9% IGROGTT), and 42.8% NGTOGTT subjects. When HbA1c ≥ 6.5% in older people, HbA1c shows the highest correlation with Glucose 0 min of the OGTT. When HbA1c < 6.5%, postprandial hyperglycemia is a main characteristic of older people, and HbA1c shows the highest correlation with Glucose 120 min of the OGTT.