Insulin resistance is a condition in which the body’s cells become less responsive to the effects of insulin, a hormone produced by the beta cells in the pancreas. Insulin is central for regulating blood sugar (glucose) levels, facilitating the uptake of glucose by cells for energy.
Obesity and especially metabolic syndrome are pro-inflammatory conditions, that can give rise to hypertension, dyslipidemia, insulin resistance, diabetes, and cardiovascular disease. Colchicine, an anti-inflammatory agent, is frequently used for gout, pericarditis and familial Mediterranean fever.
In this small randomized clinical trial, authors found that colchicine 0.6 mg twice daily decreased inflammatory markers CRP, ESR, WBC, and ANC in patients with obesity and metabolic syndrome. These results could provide some basis for designing outcome-driven clinical trials, such as evaluating diabetes and CVD risk reduction with colchicine.
More good news for metformin. MET-REMODEL trial tested patients with known cardiovascular disease and insulin resistance, but without gross diabetes. Patients received metformin or placebo for 12 months.
Compared to the placebo group, subjects receiving metformin experienced the following improvements in 12 months: Less left ventricular mass index, less LVM, lower systolic BP, decreased body weight and less oxidative stress.
Early start of metformin could be useful in adults with insulin resistance. Long term side effects of metformin, however, need to be discussed thoroughly with patients.
It is not always easy to distinguish LADA from type 1 or type 2 diabetes. Common parameters utilized are BMI, age, family history, HLA-typing, clinical presentation, glucose variability and severity, insulin production, C-peptide levels, as well as autoantibodies against glutamic acid decarboxylase (GAD65), pancreatic islet cells (ICA) or insulin (IAA).
The article shows that other inflammatory markers could also be useful in differentiating the diagnoses. Such markers are; adiponectin, soluble tumor necrosis factor-α receptor 2 (sTNFR2), interleukin-6 (IL-6), hs-CRP, and total leukocyte number. More research is needed on how to incorporate the additional tests in clinical practice.
Results of the article suggest that longer-acting cortisol-equivalent supplementation is more beneficial than conventional therapy with multiple daily doses of hydrocortisone in adults with adrenal insufficiency. Advantages are reduced body weight, heightened immunity, less recurrent infections, and improved quality of life. A group of 89 participants were followed for 6 months.
This is a major trial evaluating the usefulness of hydrocortisone and fludrocortisone during septic shock. About 12,000 patients were followed for 30-120 days. Compared to placebo, high doses of adrenal hormone equivalents improved 90-day death rates significantly. This is a step forward in improving the care of the deadly condition.
This case shows a positive correlation between thyroid levels and J-wave amplitude in a patient experiencing ventricular fibrillations. Pronounced J-waves in multiple EKG leads can predict lethal arrhythmias, thus early diagnosis and treatment are necessary. More research would be needed however to clarify or solidify the cause-effect dance between hyperthyroidism and elevated J-waves.
CANTOS trial shows that specific inhibition of interleukin-1β leads to lower hsCRP levels and cardiovascular events in 1 and 4 years respectively. A group of 10,000 participants with established myocardial infarction and elevated hsCRP > 2 mg/L were randomized to receive canakinumab, a specific anti- IL1β monoclonal antibody, or placebo.
Cardiovascular benefits (17% event reduction) were seen with canakinumab 150 mg compared to control subjects, irrespective of lipid profile trends. Other significant clinical outcomes among patients receiving canakinumab were; more pseudo-membranous colitis (+233%), fatal infections and sepsis (+72%), leukopenia (+67%) and thrombocytopenia (+40%), but less fatal cancers (-30%), osteoarthritis (-28%) and gout (-53%); all consistent with the anti-inflammatory pathway of treatment.
The study supports the notion that vascular inflammation, in this case measured by IL1β-hsCRP axis, is a reversible contributor to atherosclerosis, independent of lipid measures. Participants’ baseline LDL was 82 mg/dL, with no meaningful alterations during the course of the trial.
In the setting of unforeseen adverse events of pseudo-membranous colitis, fatal infections and sepsis, leukopenia and thrombocytopenia, I anticipate that more research would be needed to FDA approve canakinumab for secondary CVD prevention in adults with statin-residual atherosclerosis risk.
Diacerein, a IL1-β inhibitor, is approved in some countries for osteoarthritis. This randomized controlled trial evaluated diacerein in adults with type 2 diabetes. A group of 84 participants receiving either diacerein or placebo were followed for 48 weeks.
The IL1-β inhibitor reduced A1c significantly by 0.6% and 0.35% at 24 and 48 weeks. Although 65% of treatment group experienced some degree of diarrhea, no major adverse events were noted.
Diacerein could be a reasonable anti-diabetic agent particularly in those with osteoarthritis. More importantly, the study gives clues to another pathogenesis route of diabetes; namely inflammation.
I anticipate that anti-inflammatory targets would be critical to the future of diabetes research.