There were no other significant differences in baseline characteristics between niacin and niacin placebo groups in participants either with or without diabetes. Following randomization, HDL-C levels continued to increase and triglycerides decreased further in participants both with and without diabetes randomized to active niacin.
Table 2 summarizes the baseline and treatment lipoprotein values by diabetes status and niacin treatment assignment.
Niacin treatment resulted in significant decreases in LDL-C and triglycerides, and increased HDL-C compared with placebo control for participants both with and without diabetes.
Fasting glucose and HbA 1c levels were monitored as indices of glycemic status during niacin treatment. Table 3 presents the glucose, HbA 1c , and uric acid levels at baseline and the average of 6 postrandomization values. Niacin use resulted in a small but statistically significant increase in average glucose levels in participants both with 8.
Figure 3 depicts the course of glucose values during the niacin treatment period. Niacin use also resulted in a small but statistically significant difference in change in HbA 1c levels 0. The response of neither HbA 1c nor glucose levels to niacin was significantly affected by obesity.
The dose was lowered for 1 participant with diabetes assigned to niacin, but none had niacin discontinued. One participant with diabetes assigned to niacin and 1 without diabetes assigned to placebo had niacin discontinued due to possible gout. The effect of niacin on plasma glucose and HbA 1c levels could have been modified if hypoglycemic therapy was adjusted by primary caregivers in response to receiving reports of abnormal laboratory results. We therefore examined the frequency of insulin use and average dose of insulin used at baseline and at the final follow-up visit for participants with diabetes randomized to niacin vs those randomized to niacin placebo.
Niacin use might also have resulted in development of diabetes in patients who did not have diabetes at entry into ADMIT.
Therefore, we looked for new users of insulin or oral hypoglycemic agents among ADMIT participants who did not have diabetes at the baseline visit. Among the participants randomized to niacin treatment who did not have diabetes at baseline, only 1 reported use of oral hypoglycemic therapy at subsequent follow-up visits.
No niacin users without diabetes reported insulin use during follow-up, nor did any participants without diabetes who were randomized to niacin placebo report subsequent use of either insulin or oral hypoglycemic therapy. Other reasons for discontinuation of niacin in participants with diabetes included comorbid vascular disease, patient request, and acanthosis nigricans.
This HbA 1c limit was exceeded after randomization in 18 participants with diabetes, 10 of whom were assigned to niacin and 8 assigned to placebo. Lipid-modifying therapy is recommended in both peripheral arterial disease and diabetes to reduce the risk of atherosclerotic vascular disease. Despite its proven ability to increase HDL and lower triglycerides, the use of niacin has been discouraged in patients with diabetes, 10 - 13 largely due to reports of deterioration of glycemic control in subjects both with and without diabetes who were treated with niacin.
We therefore decided to assess the safety and efficacy of niacin use in ADMIT participants with diabetes. This report demonstrates that immediate-release niacin is equally effective in modifying lipid and lipoprotein levels in subjects with and without diabetes.
We also confirmed previous observations of increased plasma glucose levels in patients both with and without diabetes and treated with lipid-modifying doses of niacin; however, the effects observed over 60 weeks of follow-up were relatively modest and did not result in significantly increased rates of niacin discontinuation or alterations in hypoglycemic therapy.
It is important to note, however, that the results observed here might not reflect those obtained with other niacin formulations, and that glycemic therapy may have been modified in individual patients as a result of niacin treatment. Previous reports of niacin-induced glucose intolerance are derived largely from uncontrolled case reports involving small numbers of subjects.
In the present study we, in fact, observed a transient increase in plasma glucose as niacin was titrated to its maximum dose. The only other report that includes a number of subjects comparable with our own is a retrospective study of niacin use at a Department of Veterans Affairs Medical Center. In that study, niacin was administered without blinding or use of placebo controls.
Given the current perception that niacin significantly worsens glycemic status, it is possible that physician bias may have influenced the niacin discontinuation rate. Although the effect of niacin treatment on glycemic status overall was modest in ADMIT, our findings do not preclude the possibility that its use, particularly at doses higher than those used here, or using preparations other than crystalline niacin, may significantly adversely affect glycemic control in individual patients with diabetes.
Therefore, glycemic status should be carefully monitored during niacin therapy in patients with diabetes, and the dose modified or discontinued if glycemic status clearly deteriorates. In addition, plasma insulin was not measured nor was insulin resistance formally assessed in this study.
Several studies have shown decreased glucose tolerance and increased plasma insulin levels in subjects without diabetes following short-term niacin treatment. It is also possible that the changes in glycemic indices observed here, although relatively modest, might offset some of the cardiovascular risk reduction with niacin. Recently published guidelines for treatment of dyslipidemia in type 2 diabetes mellitus recommend aggressive lipid modification using statin drugs or fibrates.
Furthermore, in cases of extreme hypertriglyceridemia, combination therapy with gemfibrozil and niacin may be required to reduce triglycerides to acceptable levels. There is limited information about which of the currently available lipid-modifying interventions offer the greatest benefit for patients with diabetes in terms of reduced cardiovascular morbidity and mortality.
A recent post-hoc analysis of the Scandinavian Simvastatin Survival Study 4-S indicates that participants with diabetes experienced a significant reduction in coronary heart disease events with simvastatin therapy.
Similarly, in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial VA-HIT , participants with diabetes experienced coronary heart disease event reduction with gemfibrozil equivalent to that observed in the entire cohort. Despite current recommendations against use of niacin in diabetes, 10 , 12 the present study demonstrates that lipid-modifying doses of immediate-release niacin can be used safely in patients with stable, controlled, type 2 diabetes mellitus.
Niacin therapy may be considered as an alternative to statin drugs or fibrates in patients with diabetes in whom these agents are not tolerated, or in whom they fail to sufficiently correct hypertriglyceridemia or low HDL-C. Conversely, in view of the absence of an effect on glycemic status of statin drugs or fibrates, these agents should still be considered first-line therapy in diabetic dyslipidemia. If we combine this information with your PHI, we will treat all of that information as PHI, and will only use or disclose that information as set forth in our notice of privacy practices.
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Please try again. Because of the toxicities of niacin, and especially because of the questionable benefits in terms of preventing heart disease, I no longer have any patients on niacin.
This occurs in approximately one person for every thousand people taking statins for a year. However, in that same group, we would expect five people to have a heart attack or death prevented by taking the statin, so there is clearly more benefit than harm, if the people taking statins are of appropriate risk to do so. I agree with you that both patients and doctors need to be aware of these risks, both before deciding to take the medication and while monitoring treatment.
Roach regrets that he is unable to answer individual letters, but will incorporate them in the column whenever possible. Readers may email questions to ToYourGoodHealth med. Join our Newsletter. Nov 25, PM By: Dr.
No differences were observed in glycosuria or the addition of new diabetes medications in patients receiving niacin vs. Fasting glucose increased modestly and significantly in the niacin-treated group at one year, two years and four years. After treatment was discontinued, fasting glucose returned to baseline in the niacin-treated group but increased in the placebo group.
Subsequent analysis indicated that the long-term cardiovascular benefits of niacin outweighed any effects on glucose. Thus, when administered at doses of 2. Adverse glycemic effects seem to be most prominent during upward titration of niacin.
The effects are often transient and return to near baseline levels after a relatively short time. It appears that glycemic effects are more pronounced in patients with type 2 diabetes compared with those without diabetes. It should also be noted that most of these trials included patients with relatively well-controlled diabetes, so the glycemic effects of niacin in patients with poorly controlled diabetes may be more significant.
Niacin offers many CV benefits, and any effect on glucose can typically be accounted for with mild adjustments in diabetes therapy as necessary. Although several larger studies suggest minimal to modest long-term effects of niacin on blood glucose levels in people with type 2 diabetes, it is not clear from reading these studies if medications to control glucose were modified. In fact, the observations that glucose rose most in the earlier phases of the study and then returned toward baseline raise the possibility that the investigators increased medications to treat hyperglycemia during the trials.
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