2019 Endocrine Society Guidelines on Metabolic Risk

Endocrine Society recently published new guidelines on metabolic risk. Metabolic risk is characterized similarly to metabolic syndrome (syndrome X) but with the name change to emphasize action rather than description. Presence of three or more of the following entities defines high metabolic risk: high blood pressure, high glucose, high triglycerides, low HDLc, and increased waist circumference.

Although guidelines are similar to those of other national association such as ACC/AHA, ADA, AACE, and NLA; they introduce or emphasize the following elements:

  • Should measure waist circumference routinely.
  • Include A1c in the definition of metabolic risk (vs. fasting glucose only). 
  • Be more aggressive in using statin therapy for primary prevention. 
  • Can add fenofibrate rather than ezetimibe if triglycerides are above 200 mg/dL and HDLc is low.

These guidelines are essential as they further raise awareness of the real cardiovascular and diabetes risk associated with metabolic syndrome, and more importantly encouraging providers to act upon it.

I anticipate elaboration and incorporation of the above critical changes in other national guidelines.  Prevention, always first.


Colchicine may reduce inflammation in metabolic syndrome

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 evidence of Metformin benefits in early prediabetes

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.


Leptin improves brain insulin resistance

Leptin deficiency leads to weight gain, obesity, and insulin resistance. Leptin replacement in the form of metreleptin has been approved by the FDA for congenital or acquired generalized lipodystrophy. The current analysis reveals that metreleptin also improves central insulin sensitivity primarily via hypothalamus and to a lesser extent prefrontal cortex.


Prediabetics when diagnosed by A1c are at a higher risk of CVD and mortality

Findings are consistent with the fact that A1c is a more specific test in diagnosing prediabetes and diabetes compared to fasting plasma and 2-hour post challenge glucose tests. Increased specificity of A1c implies a more advanced state of prediabetes at diagnosis.

It is not surprising then to see that rates of cardiovascular disease and all-cause mortality are higher in prediabetics identified by A1c rather than fasting or post stress glucose levels. 


Soluble fiber helps with weight and glucose metabolism

Soluble fiber supplementation reduced BMI, body weight, body fat, fasting glucose and fasting insulin compared with the effects of placebo treatments. Isolated soluble fiber supplementation improves anthropometric and metabolic outcomes in overweight and obese adults, thereby indicating that supplementation may improve fiber intake and health in these individuals. 


Uric acid and renal failure

Uric acid elevation is frequently seen in patient with metabolic syndrome. It can lead to gout and kidney stones. In the current study, researchers monitored and analyzed a group of 4,000 participants suffering from chronic kidney disease, stages 2-4.

Authors found that higher baseline uric acid levels were a strong independent predictor of renal failure in adults with initial eGFR > 45 (stage 3a CKD), marginally in those with eGFR 30-45 (stage 3b), and not a predictor at all in subjects with eGFR < 30 (stage 4).

Future interventional studies would be useful in determinining if hyperuricemia is a causative and modifiable risk factor.


Calcium score is important in adults with diabetes and metabolic syndrome

The MESA study uncovered the significance of coronary artery calcium (CAC) score in predicting coronary events among adults with diabetes and metabolic syndrome. About 7,000 individuals without baseline CVD were followed for 11 years.

Authors found that calcium score was more important than severity or duration of diabetes in identifying patients at higher risk for coronary heart disease. CAC score was equally useful in those with metabolic syndrome and without diabetes. 

In the future I anticipate CAC score to be incorporated in the ASCVD risk calculator as an independent predictor. Such a calculator is provided by the American College of Cardiology and American Heart Association (click here). It estimates the risk of an ASCVD event in 10 years based on person’s age, gender, race, cholesterol, blood pressure and history of diabetes and smoking.


Coffee extends longevity

This major prospective study finds that coffee consumption reduces all cause mortality by 12% in men and 7% in women. About 500,000 participants were followed for 16 years.

More specifically, coffee intake seems to lower gastrointestinal death in men by 60%. In women however, the digestive, circulatory, and cerebrovascular disease mortality are reduced by 40%, 22% and 30% respectively, while raising the risk death by 30% from an ovarian cancer.

The study also uncovers the antiinflammatory effect of coffee on hepatic-insulin resistance axis, as documented by lower levels of AlkPhos, ALT, AST, GGT, CRP, Lp(a) and A1c in high consumers.

Unless side effects are present, coffee consumption promotes a good anti-inflammatory health.


Global obesity study: dismal projections

A global observational study on obesity and its related complications: about 70 million persons from 195 countries were analyzed. Study time span 1980-2015. Obesity and disease burden are on the rise, particularly among children. Cardiovascular disease is the number one killer among those with high BMI. Obesity can cause diabetes, NASH, CVD, kidney disease, musculoskeletal anomalies and various types of malignancies, primarily of GI and GU nature.

How to fix it??


Insulin Resistance and Memory

Higher fasting insulin levels and increased insulin resistance predict future memory decline as measured by verbal fluency. About 4,000 individuals, average age 50, were followed for 11 years. These findings imply the need of addressing insulin resistance early rather then later, when prediabetes or diabetes emerge.


Resveratrol, Grape and Metabolic Syndrome

Not a good news for the resveratrol supplement. Moderate doses provided no benefits while high doses increased bad cholesterol and fructosamine, a marker of blood glucose levels. This was a randomized controlled trial in middle aged men with metabolic syndrome and obesity, BMI 34. Participants were followed for 4 months.