Exercising with blocked muscle glycogenolysis: Adaptation in the McArdle mouse

Background

McArdle disease (glycogen storage disease type V) is an inborn error of skeletal muscle metabolism, which affects glycogen phosphorylase (myophosphorylase) activity leading to an inability to break down glycogen. Patients with McArdle disease are exercise intolerant, as muscle glycogen-derived glucose is unavailable during exercise. Metabolic adaptation to blocked muscle glycogenolysis occurs at rest in the McArdle mouse model, but only in highly glycolytic muscle. However, it is unknown what compensatory metabolic adaptations occur during exercise in McArdle disease.

The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis

Inflammatory arthritides are chronic diseases characterised by an increase in cardiovascular risk, largely attributable to the synergy between high-grade systemic inflammation and an elevated prevalence of traditional cardiovascular risk factors. Amongst the latter, insulin resistance and type 2 diabetes (T2D) play a key position. Previous studies demonstrated a potential insulin-sensitizing effect of anti-TNF biologic medications. For converse, less is known about the role of newer biologics or small molecules. For this reason, we performed a systematic review of the literature in order to identify the available data on the effect on insulin resistance of non-TNF targeting biologics and small molecules approved for the treatment of inflammatory arthritides. The search strategy initially retrieved 486 records of which only 10 articles were selected for inclusion in the final review. According to the available evidence, some of the newest molecules, in particular tocilizumab and abatacept, may have a role in improving insulin sensitivity; for converse, anakinra-mediated effect on glucose metabolism may exploit different facets of T2D pathophysiology, such as the preservation of beta-cell function. However, the data available on this issue are largely inconsistent and future, adequately designed studies are still needed to clarify the differential impact of novel therapeutics on individual pathophysiological features of T2D and other emerging cardiovascular risk factors.     

Role of insulin receptor substrate‐1 for diethylnitrosamine plus high‐fat diet‐induced hepatic tumorigenesis in mice

We investigated the role of insulin receptor substrate (Irs)‐1 for diethylnitrosamine (DEN) plus high‐fat (HF) diet‐induced hepatic tumorigenesis in mice. We gave DEN by intraperitoneal injection at the dose of 80 mg/kg to 18‐week‐old wild‐type (WT) and Irs1‐knockout (Irs1^−/−) mice, which were fed a HF diet from 8 weeks‐of‐age until they were killed (52 weeks). The Irs1^−/− mice showed significantly lower plasma alanine aminotransferase levels, triglyceride contents in the liver and also lower expression levels of the genes encoding inflammatory cytokines than the WT mice. The incidence of DEN plus HF diet‐induced hepatic tumors was 71.4% in the WT mice, whereas it was just 14.3% in the Irs1^−/− mice. The present study showed that Irs1 played an important role in DEN plus HF diet‐induced hepatic tumorigenesis.     

Intensive insulin therapy: enhanced Model Predictive Control algorithm versus standard care

Objective  To investigate the effectiveness of an enhanced software Model Predictive Control (eMPC) algorithm for intravenous insulin infusion, targeted at tight glucose control in critically ill patients, over 72 h, in two intensive care units with different management protocols. Design  Comparison with standard care in a two center open randomized clinical trial. Setting  Two adult intensive care units in University Hospitals. Patients and participants  Thirty-four critically ill patients with hyperglycaemia (glucose >120 mg/dL) or already receiving insulin infusion. Interventions  Patients were randomized, within each ICU, to intravenous insulin infusion advised by eMPC algorithm or the ICU’s standard insulin infusion administration regimen. Measurements and results  Arterial glucose concentration was measured at study entry and when advised by eMPC or measured as part of standard care. Time-weighted average glucose concentrations in patients receiving eMPC advised insulin infusions were similar [104 mg/dL (5.8 mmol/L)] in both ICUs. eMPC advised glucose measurement interval was significantly different between ICUs (1.1 vs. 1.8 h, P < 0.01). The standard care insulin algorithms resulted in significantly different time-weighted average glucose concentrations between ICUs [128 vs. 99 mg/dL (7.1 vs. 5.5 mmol/L), P < 0.01]. Conclusions  In this feasibility study the eMPC algorithm provided similar, effective and safe tight glucose control over 72 h in critically ill patients in two different ICUs. Further development is required to reduce glucose sampling interval while maintaining a low risk of hypoglycaemia. An erratum to this article can be found at     

Systematic review and meta-analysis of diabetes specialist delivered insulin education for adults with type 2 diabetes in outpatient settings

ObjectiveWe conducted a systematic review and meta-analysis of insulin education for people with type 2 diabetes to assess its effectiveness in improving glycaemic levels.MethodsWe searched the following online databases from the earliest record to 17 February 2020: MEDLINE, EMBASE, PsycINFO, CINAHL, Web of science, Cochrane Library and https://clinicaltrials.gov. Data was extracted on publication status, participants’ characteristics at baseline, intervention and control group, study design, and data for primary and secondary outcomes, change in HbA1c(%), change in weight (Kilogram). The review was registered with international prospective register of systematic reviews registration (PROSPERO):CRD42020167769.ResultsEighteen papers were included in the systematic review. In the meta-analysis there was a small statistically significant improvement in HbA1c (0.39% points/4.4 mmol/mol reduction) in the insulin education group compared to control conditions (N = 10 studies, n = 3307 participants, SMD = ?0.22, 95% CI = ?0.34, ?0.10, I² = 66% p = 0.002). There was a small non-significant increase in weight (0.54 Kg) in the insulin education group compared to control conditions (N = 6 studies, n = 470 participants, SMD = 0.03, 95% CI = ?0.10, 0.17, I² = 0.0%, p = 0.82). Quality of evidence was rated low to very low.ConclusionsEnhanced insulin education delivered by diabetes specialists is potentially more effective than standard care. Further research is required to reach robust conclusions.     

Insulin and HOMA in Spanish prepubertal children: relationship with lipid profile

OBJECTIVE: The effects of insulin or insulin resistance on the lipid profile seem to change with age. The aim of this study was to analyze insulin levels and an insulin resistance index and to investigate the relationship between these and the lipid profile in a population-based sample of Spanish prepubertal children. METHODS: 1048 (524 boys and 524 girls) randomly selected prepubertal children were studied. Children were 6 to 8 years old with a mean age of 6.7. Plasma lipid, FFA and insulin levels were measured. The homeostatic model assessment (HOMA) was calculated as an indicator of insulin resistance. RESULTS: When analyzing percentile values of insulin, HOMA and FFA by sex, we observed that girls had significantly higher insulin concentrations than boys (except at the 10th percentile) and significantly higher FFA (except at the 90th percentile) with no significant differences between sexes for HOMA. Multivariate regression analyses showed that insulin was positively associated with glucose, triglycerides and apoB in boys but not in girls, and negatively associated with FFA in both genders. CONCLUSIONS: We report here data about the distribution of insulin in the Spanish prepubertal population. The higher levels of insulin in prepubertal girls could indicate that girls start to be more insulin resistant than boys at this age, although other manifestations of insulin resistance are not yet detectable.     

Fatty acid composition of erythrocyte phospholipids is related to insulin levels, secretion and resistance in obese type 2 diabetics on Metformin

BACKGROUND: Relationships between fatty acids in erythrocyte phospholipids and insulin parameters have been described in healthy and overweight individuals, but not in obese diabetics. We assessed whether erythrocyte phospholipid fatty acids are related to insulin parameters in obese type 2 diabetics on Metformin. METHODS: In 23 diabetics, the fractions of the different fatty acids in erythrocyte phospholipids were correlated with insulin levels, secretion, sensitivity, resistance and insulinemic response following a standardised breakfast. RESULTS: Fasting insulin levels and insulin resistance correlated positively with the fraction of alpha-linolenic and dihomo-gamma-linolenic acid and with the ratios of stearic to palmitic and dihomo-gamma-linolenic to linoleic acid and negatively with the fraction of palmitic acid in erythrocyte phospholipids. Insulin secretion correlated negatively with the fraction of palmitic acid. For this parameter, a positive correlation was also found with the sum of uneven fatty acids. Insulinemic response following a meal was negatively associated with the fraction of oleic acid in erythrocyte phospholipids. Insulin sensitivity did not correlate with erythrocyte fatty acids. CONCLUSIONS: The relationships found differ from those described in healthy and overweight individuals and may be characteristic for type 2 diabetics. They concur with the recommendations that saturated fat intake should be reduced and monounsaturated increased.