The Long-Term Response of Diabetes Mellitus to Salicylate Therapy

Gilgore, Sheldon G.; Rupp, J. J.

doi:10.1001/jama.1962.03050140067017c

Cited by 11 publications

(5 citation statements)

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“…This change was particularly impressive as glucose levels were only slightly above normal at baseline and the reduction occurred without hypoglycaemia. Our finding is consistent with previous reports of glucose-lowering effects of aspirin and salsalate in both diabetic [4–6, 14, 16, 17] and prediabetic [18, 19, 23] individuals.…”

Section: Discussionsupporting

confidence: 94%

A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance

et al. 2013

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Aims/hypothesis Chronic sub-acute inflammation contributes to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. High doses of salicylate reduce inflammation, glucose and triacylglycerols, and may improve insulin sensitivity, suggesting therapeutic potential in impaired fasting glucose and/or impaired glucose tolerance. This trial aimed to evaluate the effect of salsalate vs placebo on insulin resistance and glycaemia in impaired fasting glucose and/or impaired glucose tolerance. Methods We conducted a 12 week, two-centre, randomised, placebo-controlled study to evaluate the effect of salsalate (up to 4 g/day) vs placebo on systemic glucose disposal. Secondary objectives included treatment effects on glycaemia, inflammation and cardiovascular risk factors. Seventy-eight participants with impaired fasting glucose and/or impaired glucose tolerance from two VA healthcare systems were enrolled. Randomisation assignment was provided by the coordinating center directly to site pharmacists, and participants and research staff were blinded to treatment assignment. Results Seventy-one individuals were randomised to placebo (n = 36) or salsalate (n = 35). Glucose disposal did not change in either group (salsalate 1% [95% CI −39%, 56%]; placebo 6% [95% CI −20%, 61%], p = 0.3 for placebo vs salsalate). Fasting glucose was reduced by 6% during the study by salsalate (p = 0.006) but did not change with placebo. Declines in glucose were accompanied by declines in fasting C-peptide with salsalate. Insulin clearance was reduced with salsalate. In the salsalate group, triacylglycerol levels were lower by 25% (p = 0.01) and adiponectin increased by 53% (p = 0.02) at the end of the study. Blood pressure, endothelial function and other inflammation markers did not differ between groups. Adipose tissue nuclear factor κB (NF-κB) activity declined in the salsalate group compared with placebo (−16% vs 42%, p = 0.005), but was not correlated with metabolic improvements. The frequency of tinnitus was low but tended to be higher with salsalate therapy (n =4 vs n =2). Conclusions/interpretation In summary, salsalate therapy was well tolerated, lowered fasting glucose, increased adiponectin and reduced adipose tissue NF-κB activity. These changes were not related to changes in peripheral insulin sensitivity, suggesting additional mechanisms for metabolic improvement. Trial registration ClinicalTrials.gov NCT00330733 Funding Office of Research and Development, Medical Research Service, Department of Veterans Affairs and NIH K24 DK63214

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Section: Discussionsupporting

confidence: 94%

A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance

et al. 2013

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“…83, 84 Interestingly, after nearly a half century, there has been a recent resurgence in studies on the utility of salicylate, which acts directly at the site of inflammation to reduce COX-1 and COX-2 expression, as a T2D therapeutic. 85, 86 …”

Section: The Ep3 Receptor: Targeting Dysfunctional Agonist Productionmentioning

confidence: 99%

Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes

et al. 2014

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The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology.

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“…Indeed, not only do salicylates reduce fasting systemic glucose concentrations, they also improve systemic glucose concentrations following oral glucose, a mixed meal and an intravenous insulin challenge in diabetic and non-diabetic patients [9-14]. Moreover, in diabetic and non-diabetic patients, improvement of glucose tolerance was observed within 1 week of treatment with aspirin (chemically, acetylsalicylic acid) [10, 12].…”

Section: Introductionmentioning

confidence: 99%

The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study

et al. 2008

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Aim/hypothesis Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. Methods The study was a randomised, double-blind, placebocontrolled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI≥30 kg/m 2 . The intervention was salsalate (3 g/day, n=28) or identical placebo (n=26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal (R d ) by euglycaemic-hyperinsulinaemic clamp (insulin infusion rate 40 mU m −2 min −1) and glucose tolerance by 75 g OGTT. ResultsThe study was completed by 47 participants, of which 40 were analysed (salsalate n=22, placebo n=18

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The Long-Term Response of Diabetes Mellitus to Salicylate Therapy

Cited by 11 publications

References 0 publications

A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance

A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance

Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes

The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study

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