Hypertriglyceridaemia-related Risk in Diabetes
Compelling evidence suggests that hypertriglyceridaemia increases CVD risk in diabetes. For instance, Schulze et al. followed 921 women with type 2 diabetes who did not show CVD at baseline for 10 years. Of these, 122 women developed incident CHD. At baseline, the mean age (60.6 years) and the mean fasting triglyceride level (2.56 mmol/L) among women who developed CHD differed significantly from those who remained free of CHD (58.0 years; 2.15 mmol/L). The relative risk of CHD (adjusted for various confounders including age, hypertension, BMI and aspirin use) showed a trend towards an increased risk from low (median 0.98 mmol/L) to high (median 3.45 mmol/L) levels of fasting triglycerides (relative risk 1.42; 95% CI 0.79–2.54), although this was not statistically significant. High levels of fasting triglycerides increased CVD risk among women with low HbA1C concentrations. The relative CVD risk comparing the bottom and top fasting triglyceride tertiles was 3.32. This association was not present among women with high HbA1C concentrations (figure 1), possibly suggesting that poor glycaemic control may mask the effects of HDL and triglyceride levels.
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Figure 1.
Relative risk of coronary heart disease by tertiles of HbA1C (%) and fasting triglycerides (mmol/L)
Key: HbA1C = glycated haemoglobin A1C
Laakso et al. followed 153 men (mean age 56 years) and 160 women (mean age 58 years) with non-insulin-dependent diabetes for up to seven years. Total triglyceride levels >2.3 mmol/L approximately doubled the risk of age-adjusted death from CHD (OR 2.2; 95% CI 1.2–4.0) and all CHD events (OR 1.6; 95% CI 1.0–2.8) compared with lower concentrations. The independent association between total triglycerides and CHD events disappeared on multivariate logistical regression analysis that controlled for high LDL (<4.3 mmol/L) and HDL (>1.2 mmol/L). However, in patients with low LDL-cholesterol (≤4.3 mmol/L; unstandardised β-coefficient 1.0266) and low HDL-cholesterol (≤1.12 mmol/L; unstandardised β-coefficient 0.8129) VLDL triglycerides were significantly associated with CHD events, suggesting an independent relationship.
The Strong Heart Study followed 2,108 Native Americans with type 2 diabetes and 2,060 non-diabetic controls, all of whom were free from CVD at baseline. After an average of 9 years, 521 and 145 of the diabetic and non-diabetic patients respectively had developed CVD. Based on a Cox multivariate regression model, compared with triglyceride levels <1.20 mmol/L, men with concentrations of 1.20–1.98 mmol and >1.98 mmol were 40% (95% CI 0.94–2.07) and 39% (95% CI 1.00–1.98) respectively more likely to develop CVD, after adjusting for several non-lipid confounding variables such as age, BMI, HbA1C and insulin use. Compared with triglyceride levels <1.28 mmol/L, women with concentrations of 1.28–1.98 mmol and >1.98 mmol were 36% (95% CI 0.99-–1.87) and 61% (95% CI 1.17–2.22) respectively more likely to develop CVD.
Diabetes and Pancreatitis
Chronic pancreatitis causes between 0.5% and 1% of cases of diabetes, and between 40% and 60% of patients with chronic pancreatitis, show concurrent diabetes. Hypertriglyceridaemia may partly account for this overlap. Indeed, hypertriglyceridaemia causes up to 10% of acute pancreatitis and up to half of gestational pancreatitis cases. The mechanism linking hypertriglyceridaemia and pancreatitis remains unclear. However, an increase in pancreatic free fatty acid levels could induce inflammation. Alternatively, hyperviscosity due to elevated chylomicron levels could cause capillary ischemia and acidosis.
Hypertriglyceridaemia tends to be a primary cause of pancreatitis only at relatively high concentrations. In a Canadian study, 15 of 95 patients (mean age 54.2 years; 73.7% male; 41.1% with diabetes) presenting with non-acute pancreatitis showed triglyceride levels >20 mmol/L (mean 38.1 mmol/L). In contrast, none of the control group of 91 patients showed pancreatitis despite triglyceride levels between 10 and 20 mmol/L.