Does Elevated Triglycerides Disturb Glucose Metabolism?
Yes, elevated triglycerides directly disturb glucose metabolism through multiple mechanisms, including inducing insulin resistance, impairing beta-cell function, and promoting ectopic fat deposition in metabolically active tissues.
Bidirectional Relationship Between Triglycerides and Glucose Metabolism
The relationship between triglycerides and glucose metabolism operates in both directions, creating a vicious cycle:
Triglycerides Cause Insulin Resistance and Glucose Dysregulation
Elevated plasma triglycerides predict the development of type 2 diabetes over time, with the effect appearing independent of and potentially greater than that of elevated non-esterified fatty acids (NEFA) alone 1
Short-term increases in plasma triglycerides induced by either intravenous lipid infusion or high-fat diet produce deterioration of glucose control 1
Chronic lowering of plasma triglycerides by fibrates improves glucose homeostasis and may prevent type 2 diabetes 1
In insulin-treated patients with type 2 diabetes, elevated triglyceride levels are strongly associated with inadequate glycemic control, with adjusted odds ratios of 3.12 for HbA1c ≥7.0% when triglycerides are ≥3.40 mmol/L (≥301 mg/dL) compared to triglycerides <1.70 mmol/L (<150 mg/dL) 2
Mechanisms of Triglyceride-Induced Glucose Disturbance
Intracellular deposition of triglycerides in muscles, liver, and pancreas attenuates glucose metabolism by interfering with insulin signaling and insulin secretion 3
Ectopic triglyceride accumulation in pancreatic beta-cells results in beta-cell dysfunction, impairing insulin secretion 3
Central (visceral) adipocytes exhibit high rates of basal lipolysis and flood the portal circulation with free fatty acids at metabolically inappropriate times, exposing non-adipose tissues to fat excess and leading to insulin resistance 3
Excessive glucose intake induces insulin resistance through activation of the transcription factor ChREBP (carbohydrate response element binding protein), which leads to counterproductive increases in hepatic glucose production 4
Glucose Metabolism Causes Triglyceride Elevation (The Reverse Direction)
When glucose is administered in excess of what can be directly oxidized for energy production and glycogen synthesis, the excess is directed to lipogenesis, promoting fat deposition 4
High carbohydrate feeding leads to increased total VLDL triglyceride secretion rate from de novo synthesis, primarily due to stimulation of secretion of preformed fatty acids 4
High carbohydrate intake, both in hypercaloric and eucaloric conditions, leads to lipogenesis 4
Fructose metabolism is relatively unregulated compared to glucose metabolism, and fructose enhances lipogenesis and triglyceride synthesis 4
Dietary fructose intakes exceeding 100 g/day reveal a dose-related increase in plasma triglycerides 4
Clinical Evidence of the Triglyceride-Glucose Connection
In normotriglyceridemic subjects, there is a direct correlation between insulin resistance, insulin response to food, VLDL-triglyceride secretion rate, and plasma triglyceride concentration 5
Mean triglyceride levels have risen in the United States since 1976, in concert with the growing epidemic of obesity, insulin resistance, and type 2 diabetes mellitus 4
Elevated serum triglycerides commonly associate with insulin resistance and represent a valuable clinical marker of the metabolic syndrome 6
The metabolic syndrome manifests atherogenic dyslipidemia (elevated triglycerides, increased small LDL, decreased HDL), increased blood pressure, elevated plasma glucose, and a prothrombotic state 4, 6
Clinical Implications for Management
Suppressing triglyceride levels may attain more optimal glycemic control in patients with type 2 diabetes mellitus 2
Limiting added sugars to ≤10% of total energy intake minimizes triglyceride elevation, with the lowest triglyceride levels observed at this threshold 4
Limiting fructose intake is particularly important in patients with borderline or elevated triglyceride levels, as doses above 50-100 g/day show dose-dependent triglyceride increases 4
In diabetic patients with hypertriglyceridemia, fish oil supplementation may lower triglycerides, though LDL cholesterol must be monitored as it may rise by 5-10% 4, 7
Common Pitfalls to Avoid
Do not dismiss elevated triglycerides as merely a consequence of poor glucose control—the relationship is bidirectional and triglycerides directly impair glucose metabolism 1, 3
Do not overlook the role of dietary carbohydrate quality and quantity, particularly fructose and added sugars, in driving both triglyceride elevation and glucose dysregulation 4
Do not ignore triglyceride levels in patients with diabetes, as they represent both a marker of metabolic dysfunction and a therapeutic target for improving glycemic control 2
Avoid excessive glucose intake in critically ill patients, as it exacerbates dyslipidemia and may induce insulin resistance 4