Impact of Fasting Triglycerides on CV & Diabetes Risk

High fasting triglycerides (TG), with a cutoff of ≥1.7 mmol/L, could serve as an indicator of risk for developing coronary heart disease (CHD) and T2DM, according to a study published online in DiabetesResearch and Clinical Practice.¹

“The results validate the notion that a simple measurement of plasma TG concentration can divide subjects who do not have diabetes into subgroups differing substantially in terms of magnitude of insulin-mediated glucose disposal and cardio-metabolic risk profile,” wrote first author Fahim Abbasi, MD, of Stanford University School of Medicine (Stanford, CA), and colleagues.

“Furthermore, our findings demonstrate that a plasma TG concentration ≥1.7 mmol/L is able to stratify individuals on the basis of differences in insulin sensitivity and cardio-metabolic risk profile, irrespective of their having NFG [normal fasting glucose] or PreDM [pre-diabetes],” they continued.

Individuals with prediabetes have varying degrees of insulin resistance and cardiometabolic risk.  However, studies have failed to support whether fasting plasma glucose (FPG) can be used as an indicator of cardiovascular risk. On the other hand, at least one past study has linked insulin resistance (but not FPG) to increased cardiovascular risk.² Past work by Abbasi and colleagues has suggested that a fasting TG cutoff of ≥1.7 mmol/L (≥150 mg/dl) could identify insulin resistance and cardiometabolic risk in people with hypercholesterolemia but without diabetes.³

The cross-sectional study aimed to look at this cutoff in individuals both with prediabetes and normal fasting glucose (NFG). It included 587 participants recruited for various studies about insulin resistance at Stanford Medical Center between 1996 and 2014. Participants were not on any lipid-lowering or antihyperglycemic medications, or had a FPG ≥7.0 mmol/L. The study included 370 individuals with NFG, and 217 with pre-diabetes. They separated participants into four groups: (1) NFG, TG < 1.7 mmol/L (n=259); (2) NFG, TG ≥1.7 mmol/L (n=111); (3) prediabetes, TG < 1.7 mmol/L (n=135); and (4) prediabetes, TG ≥1.7 mmol/L (n=82).

Insulin resistance was assessed by measuring steady-state plasma glucose (SSPG) concentrations during an insulin suppression test after an overnight fast. Higher SSPG concentration indicates greater insulin resistance. Participants who had an SSPG concentration in the upper 30% of the sample were considered insulin resistant, and the cutoff was defined as 10.8 mmol/L. Researchers also evaluated conventional CHD risk factors.

Key Results:

• Insulin resistance: Significantly higher in the prediabetes group with TG concentration ≥1.7 mmol/L, compared to the other three groups (P<0.001)

♦ NFG, TG < 1.7 mmol/L: 18% insulin resistant (mean SSPG 6.9)

♦ NFG, TG ≥1.7 mmol/L: 39% insulin resistant (mean SSPG 9.3)

♦ Prediabetes, TG < 1.7 mmol/L: 39% insulin resistant (mean SSPG 9.3)

♦ Prediabetes and TG ≥1.7 mmol/L: 66% insulin resistant (mean SSPG 11.3)

• CHD risk: Participants with NFG or prediabetes and with TG ≥1.7 mmol/L had a significantly more adverse CHD risk profile than those with TG < 1.7 mmol/L

♦ The findings remained significant after adjusting for age, sex, race/ethnicity, and BMI (P<0.04)

 ♦ The prediabetes group had a more adverse CHD risk profile than the NFG group

“[O]ur findings indicate that a plasma TG concentration ≥1.7 mmol/L identifies a subgroup of patients with prediabetes who fit that category [of increased insulin resistance and increased cardiometabolic risk], thereby justifying a more intensive clinical program aimed at enhancing insulin sensitivity and improving the cardio-metabolic profile,” the authors suggested.

Limitations include data drawn from other studies with differing protocols. Also, the definition of insulin resistance was based on the upper third of the study population with the most insulin resistance, and may be considered arbitrary. The definition of NFG and prediabetes were based on measurements of FPG concentration. Different classifications may have resulted if oral glucose tolerance tests were used. Finally, participants were mainly of European origin, and the results may not generalize to more diverse populations.

Nevertheless, the authors concluded, “[W]e believe that the issues addressed in our report are important, and would urge investigators with appropriately sized databases to test the possibility that incident CHD is unequivocally increased in patients with prediabetes who also have a plasma TG concentration ≥1.7 mmol/L.”

Take-home Points

• Individuals with prediabetes have varying degrees of insulin resistance and cardiometabolic risk.

• Studies have failed to support whether fasting plasma glucose (FPG) can be used as an indicator of cardiovascular risk, although there is some indication that insulin resistance may be an indicator of cardiovascular risk.

• A Stanford study found significantly higher insulin resistance in individuals with prediabetes and TG concentration ≥1.7 mmol/L.

• A TG cutoff of TG ≥1.7 mmol/L identified participants with NFG or prediabetes who were at increased CHD risk.

• Patients with TG ≥1.7 mmol/L and prediabetes may need more intensive lifestyle interventions.

The authors report no conflicts of interest.

References:

1. Abbasi F, et al. Hypertriglyceridemia: a simple approach to identify insulin resistance and enhanced cardio-metabolic risk in patients with prediabetes. Diabetes Res Clin Pract. 2016 Aug 6;120:156-161.

Faerch K, et al. Does insulin resistance drive the association between hyperglycemia and cardiovascular risk? PLoS One. 2012;7:e39260.

Abbasi F, Reaven GM. Statin-induced diabetes: how important is insulin resistance? J Intern Med. 2015 Apr;277(4):498-500.