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Dear Sir,We sincerely thank Professor Gerald Reaven for his kind response to our article on nonfasting cholesterol and triglycerides and their association with risk of myocardial infarction and total mortality [1]. We particularly appreciate the insightful discussion of potential explanations for some of our findings.

We agree that insulin resistance could be an important factor in understanding our data. Unfortunately, however, we did not measure indicators of insulin resistance or plasma insulin levels in the Copenhagen City Heart Study, and we regret that it is not possible to do so at the present time. Nevertheless, we have baseline information on whether or not the participants suffered from diabetes mellitus, and we have data on nonfasting plasma glucose levels for all participants. In our original analysis, we did not exclude participants with diabetes, nor did we a priori adjust for diabetes [1]; however, in a previous analysis, we adjusted for several factors including diabetes and found similar results for nonfasting triglycerides [2].

To try to understand whether diabetes could be the reason for the increased risk of early death with increasing levels of nonfasting triglycerides, we also carried out further analyses. The left side of Fig. 1 shows the hazard ratios for early death with increasing levels of nonfasting triglycerides in the entire study group as in the original report [1], whilst the right shows corresponding hazard ratios for the same group after exclusion of the 3% of individuals who suffered from diabetes mellitus at baseline at the 1976–1978 examination. Participants with diabetes mellitus were defined as those who informed us that they had the disease, those who were treated with antidiabetic medication and/or those with a nonfasting plasma glucose level above 11 mmol L−1.

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Figure 1. Multivariate adjusted hazard ratios for early death from any cause by increasing levels of nonfasting triglycerides in the entire study group (left) and after exclusion of diabetic subjects (right). Hazard ratios (and 95% confidence intervals) adjusted for age, hypertension, smoking, alcohol intake, lipid-lowering therapy, menopausal status (women only) and hormone-replacement therapy (women only) are shown for 7581 women and 6391 men from the Copenhagen City Heart Study with up to 31 years of follow-up.P-values for trend tests examined whether increasing levels of nonfasting triglycerides are associated with increasing risk of early death.

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The proportion of participants with nonfasting triglycerides of <1.0, 1.0–1.99, 2.0–2.99, 3.0–3.99, 4.0–4.99 and ≥5.0 mmol L−1 was very similar in the entire study group compared with the group in which diabetic participants were excluded (Fig. 1, compare left and right). Amongst women, the proportions of participants with these nonfasting triglyceride levels were 29%, 53%, 13%, 3%, 1% and 1%, respectively, in both the entire group and the group in which diabetic subjects were excluded. Amongst men, the corresponding proportions were 14%, 47%, 22%, 9%, 4% and 4%, respectively, in the entire study group and 15%, 47%, 22%, 8%, 4% and 4%, respectively, in the group in which diabetic subjects were excluded. These data show that diabetes is not the sole factor explaining elevated nonfasting triglycerides in this cohort; however, we cannot exclude the possibility that undiagnosed diabetes and insulin resistance in other participants could explain an additional proportion of those with elevated triglyceride levels.

As also shown in Fig. 1, hazard ratios for early death still increased with increasing levels of nonfasting triglycerides in both women and men when diabetic participants were excluded (Fig. 1 right). Therefore, the findings suggest that the increasing risk of early death cannot be explained by diabetes per se. However, we cannot exclude Professor Reaven’s suggestion that undiagnosed diabetes and insulin resistance may be part of the explanation for the observed association between elevated nonfasting triglycerides and early death. We fully agree that this possibility would be interesting to investigate in future studies.

Of note, with regard to the end-point of early death, stepwise elevated levels of nonfasting triglycerides are also associated with a stepwise increasing risk of ischaemic stroke in this cohort of 14 000 men and women from the Copenhagen City Heart Study followed for 30 + years, whereas increasing levels of nonfasting cholesterol are not (except for men with plasma cholesterol ≥9 mmol L−1) [3, 4]. It would also be important to understand the influence of diabetes and insulin resistance as a part of the explanation for these findings on ischaemic stroke risk.

Conflict of interest statement

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No conflict of interest was declared.

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