Long-chain omega-3 fatty acids belong to a family of polyunsaturated fatty acids that are known to have important beneficial effects on metabolism and inflammation. Such effects may confer a benefit ...in specific chronic noncommunicable diseases that are becoming very prevalent in Westernized societies e.g., nonalcoholic fatty liver disease (NAFLD). Typically, with a Westernized diet, long-chain omega-6 fatty acid consumption is markedly greater than omega-3 fatty acid consumption. The potential consequences of an alteration in the ratio of omega-6 to omega-3 fatty acid consumption are increased production of proinflammatory arachidonic acid-derived eicosanoids and impaired regulation of hepatic and adipose function, predisposing to NAFLD. NAFLD represents a spectrum of liver fat-related conditions that originates with ectopic fat accumulation in liver (hepatic steatosis) and progresses, with the development of hepatic inflammation and fibrosis, to nonalcoholic steatohepatitis (NASH). If the adipose tissue is inflamed with widespread macrophage infiltration, the production of adipokines may act to exacerbate liver inflammation and NASH. Omega-3 fatty acid treatment may have beneficial effects in regulating hepatic lipid metabolism, adipose tissue function, and inflammation. Recent studies testing the effects of omega-3 fatty acids in NAFLD are showing promise and suggesting that these fatty acids may be useful in the treatment of NAFLD. To date, further research is needed in NAFLD to (a) establish the dose of long-chain omega-3 fatty acids as a treatment, (b) determine the duration of therapy, and (c) test whether there is benefit on the different component features of NAFLD (hepatic fat, inflammation, and fibrosis).
Measurements of 21 cm Epoch of Reionization (EoR) structure are subject to systematics originating from both the analysis and the observation conditions. Using 2013 data from the Murchison Widefield ...Array (MWA), we show the importance of mitigating both sources of contamination. A direct comparison between results from Beardsley et al. and our updated analysis demonstrates new precision techniques, lowering analysis systematics by a factor of 2.8 in power. We then further lower systematics by excising observations contaminated by ultra-faint RFI, reducing by an additional factor of 3.8 in power for the zenith pointing. With this enhanced analysis precision and newly developed RFI mitigation, we calculate a noise-dominated upper limit on the EoR structure of Δ2 ≤ 3.9 × 103 mK2 at k = 0.20 h Mpc−1 and z = 7 using 21 hr of data, improving previous MWA limits by almost an order of magnitude.
Diabet. Med. 29, 1098–1107 (2012)
Non‐alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non‐alcoholic fatty liver disease is a spectrum of ...fat‐associated liver conditions that can result in end‐stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non‐alcoholic fatty liver disease and may progress to non‐alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non‐alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non‐alcoholic fatty liver disease exists in up to 70% of people with Type 2 diabetes. Non‐alcoholic fatty liver disease increases risk of Type 2 diabetes and cardiovascular disease. In people with Type 2 diabetes, non‐alcoholic fatty liver disease is the most frequent cause (∼80%) of fatty liver diagnosed by ultrasound. As non‐alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non‐alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole‐body insulin sensitivity may both contribute to prevention of Type 2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non‐alcoholic fatty liver disease and for increasing insulin resistance.
There are no approved drugs for the treatment of non-alcoholic fatty liver disease (NAFLD). However, many randomized controlled trials (RCT) have examined the effect of anti-hyperglycaemic agents on ...NAFLD in patients with and without type 2 diabetes mellitus (T2DM), since both T2DM and insulin resistance are closely linked to this burdensome liver disease.
We systematically searched publication databases using predefined keywords to identify head-to-head or placebo-controlled RCTs (published until September 30, 2019) of NAFLD individuals testing the efficacy of anti-hyperglycaemic drugs to specifically treat NAFLD or non-alcoholic steatohepatitis (NASH). Outcomes of interest included changes in serum liver enzyme levels, liver fat, liver fibrosis, or histologic resolution of NASH.
We included 29 RCTs involving a total of 2,617 individuals (∼45% had T2DM) that have used metformin (n=6 studies), glitazones (n=8 studies), glucagon-like peptide-1 receptor agonists (n=6 studies), dipeptidyl peptidase-4 inhibitors (n=4 studies) or sodium-glucose cotransporter-2 inhibitors (n=7 studies) to treat NAFLD. Although most anti-hyperglycaemic drugs improved serum liver enzyme levels, only glitazones (especially pioglitazone) and liraglutide showed an improvement of histologic features of NAFLD, with a mild beneficial effect also on liver fibrosis for pioglitazone only.
RCT evidence supports the efficacy of some anti-hyperglycaemic agents (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with pioglitazone may warrant caution. Further well-designed RCTs are needed to better characterize the efficacy and safety of monotherapy and combination therapy with anti-hyperglycaemic agents in patients with NAFLD.
Summary
We conducted a scoping review to identify definitions of metabolically healthy obesity (MHO), describe gaps in the literature, and establish a universal definition of MHO in children. We ...searched electronic databases from January 1980 to June 2017 and grey literature. Experimental, quasi‐experimental, or observational studies were eligible for inclusion if they (i) included a definition of MHO that identified risk factors, cut‐off values, and the number of criteria used to define MHO, and (ii) classified 2–18 year olds as overweight or obese. Two reviewers independently screened 1,711 papers for relevance and quality; we extracted data from 39 individual reports that met inclusion criteria. Most (31/39; 79%) definitions of MHO included an absence of cardiometabolic risk factors. Heterogeneity across MHO definitions, obesity criteria, and sample sizes/characteristics resulted in variable prevalence estimates (3–80%). Finally, we convened an international panel of 46 experts to complete a 4‐round Delphi process to generate a consensus‐based definition of MHO. Based on consensus (≥ 80% agreement), our definition of MHO included: high density lipoprotein‐cholesterol > 40 mg/dl (or > 1.03 mmol/l), triglycerides ≤ 150 mg/dl (or ≤ 1.7 mmol/l), systolic and diastolic blood pressure ≤ 90th percentile, and a measure of glycemia. This definition of MHO holds potential universal value to enable comparisons between studies and inform clinical decision‐making for children with obesity.
Abstract Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liver-related mortality and morbidity. Over the last 10 ...years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes.
•It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19).•We found that diabetes was associated with an approximately ...4-fold increased risk of having severe/critical COVID-19 illness.•This association was independent of age, sex, obesity, hypertension and smoking.•These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.
The metabolic syndrome (MetS) represents a combination of cardiometabolic risk determinants including obesity (central adiposity), insulin resistance, glucose intolerance, dyslipidaemia, ...non-alcoholic fatty liver disease and hypertension. MetS is rapidly increasing in prevalence worldwide as a consequence of the continued obesity "epidemic", and as a result will have a considerable impact on the global incidence of cardiovascular disease and type 2 diabetes. Currently, there is debate concerning whether the risk of cardiovascular disease is greater in patients diagnosed with MetS than that of the sum of the individual risk factors. At present, no unifying origin that can explain the pathogenesis of MetS has been identified and therefore no unique pharmacological treatment is available. This review summarises and critically evaluates the current clinical and scientific evidence supporting the existence of MetS as a multifactorial endocrine disease, for which maternal nutrition may be a common pathogenic mechanism. In addition, we suggest that ectopic fat accumulation (such as visceral and hepatic fat accumulation) and the proinflammatory state are central to the development of the MetS.
It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty ...liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.
As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median IQR 3.71 2.03 years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.
In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.
•NAFLD increases risk of DM in non-centrally obese subjects even after further adjustment for baseline waist circumference.•Incident DM was increased in people with the combination of fatty liver, IR and the highest quartile of FIB-4 combined, in men.•In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.
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