Comparison the Effect of Niacin Treatment with and without Atorvastatin on Lipid Profile in Type 2 Diabetic Patients

he prevalence of type 2 diabetes mellitus (T2DM) over 30 years is about 14.2% in Yazd (1). Nicotinic acid (niacin) is one of the vitamin B groups that decreases low density lipoproteins (LDL-C) and triglyceride (TG) level and increases highT 1. Professor of Endocrinology & Metabolism, Department of Internal Medicine, School of Medicine, Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 2. Assistant Professor of Cardiology, Department of Cardiology, School of Medicine, Afshar Heart Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 3. Obstetrics and Gynecology, Department of Obstetrics and Gynecology, School of Medicine, Shahid Sadoughi General Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 4. General Physician, Shahid Sadoughi University of Medical Science, Yazd, Iran. 5. Diabetes Research Center, Shahid Sadoughi University of Medical Science, Yazd, Iran.


Materials and Methods
This study is a clinical trial with cross-over method on thirty T2DM patients (9 men, 21 women) referred to Yazd diabetic research center with specific criteria. The inclusion criteria included: patient with dyslipidemia (total cholesterol > 200, LDL-C >100, TG >150, HDL-C>50 (woman) and HDL-C > 40 (men), HbA1c <10, no statin medication in past 1 month. The exclusion criteria were patient who did not use drugs and did not come to center routinely. In according to cross-over method; at first atorvastatin (20 mg/day)medication was done in 6 weeks (protocol A) and after 3 weeks as wash out period then atorvastatin (20 mg/day) with niacin (50 mg/day) for 6 weeks (protocol B) were used. Data gathering was done with a check list included demographic subject, duration, complication (nephropathy, retinopathy, neuropathy, diabetic food) and controlling of diabetes, lipid profile (TG, total cholesterol , LDL , HDL) and lab test (HbA1c, 2HPP, FBS, ALT, AST) and drug complication (dyspepsia, headache, myalgia, sever myopathy, hepatitis, rhabdomyolysis, skin flashing) before and after treatment.

Statistical analysis
Statistical analysis was doing by using SPSS for Windows, version 11.50 and kappa and paired test. Data of continuous variables showed as mean ± standard deviation. Differences between groups were showed by the paired sample tests. Statistical significance was set at P-value< 0.05.

Ethical considerations
This study was approved by Azad Islamic University of Yazd as the doctor of medicine (MD) (Code: IR.10510101852023).

Discussion
This study showed Patients treated only by atorvastatin were statistically significant for decrease total cholesterol (P-value= 0.009)  and LDL-C (P-value= 0.016) than patients treated with niacin and atorvastatin. Patients treated with atorvastatin plus niacin were statistically significant increase of HDL and decrease of TG than group give only atorvastatin (P-value= 0.08, P-value= 0.024). Lipid lowering drug use is an essential method in both patients with peripheral arterial disease and diabetic patients to reduce the risk of atherosclerotic vascular disease (13,16). in spite of ability of Niacin to increase HDL-C and lower triglycerides, the use of niacin has been weaken in patients with diabetes, (10)(11)(12)(13) due to increasing of glycemic control in patients with and without diabetes who were treated with niacin (3,(17)(18)(19).
Many article reports of niacin-induced glucose intolerance are performing on uncontrolled diabetic patients (17-20). Many of these studies were performed on patients without diabetes (18)(19)(20) and some studies conducted on patients with diabetes (3,17,21,22). One of another study showed niacin high withdrawal rates because poor glycemic control in patients with diabetes on slowrelease niacin. These data may also present a difference between sustained release and crystalline (immediate release) (23). Many studies showed decreased glucose tolerance and increased plasma insulin levels in person without diabetes after niacin administration (18,19,(22)(23)(24). A study showed minimum effect of niacin administration on insulin levels and glucose in normal person (25). For treatment of dyslipidemia in type 2 diabetes mellitus suggested offensive lipid lowering statin drugs or fibrates (12). Though LDL-C is suggested as the first goal of treatment, it is visible that hypertriglyceridemia and decreased HDL-C are very common in type 2 diabetes mellitus, and are with increased risk of atherosclerotic vascular disease (10,13). Niacin reduces plasma triglycerides by reducing hepatic production of VLDL, and increases HDL-C by up to 30%, by reducing hepatic removal of apolipoprotein A-1 (26)(27). Niacin also reduces plasma LDL-C by 10% to 15% (28). Though the LDL-C lowering of niacin may be compared with that of statin drugs, niacin has a biggest effect on HDL-C, triglycerides, and lipoprotein (a) (4). In many patients with diabetes, treatment with gemfibrozil and niacin may be need to be lower triglycerides to goals (29).
There is bounded data about lipid-modifying interventions reduce benefit for patients with diabetes for lowering cardiovascular morbidity and mortality .The Scandinavian Simvastatin Survival Study referred that patients with diabetes may be reduce coronary artery disease with simvastatin (30). In the Helsinki Heart study, patients with diabetes experienced a 60% reduction in coronary artery disease with gemfibrozil (31). In the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT), patients with diabetes may be reduce coronary artery disease with gemfibrozil (32).
In spite presence of some information about disagreeing use of niacin in diabetes (10,12) the present study suggested lipid lowering doses of immediate-release niacin can be used safely in patients with type 2 diabetes mellitus. Niacin therapy may be supplanted as recurring to statin or fibrates in patients with diabetes fail to enough effect on hypertriglyceridemia or HDL-C increasing. Remarkably in cases of lack of effect of statin and fibrates drugs, Niacin may be considered first drug for treatment of diabetic dyslipidemia. There are many drugs used for control of lipid and the best of them is most effective in decrease of cholesterol and LDL-C and increase of HDL-C. The combination therapy is used for patient with both hypertriglyceridemia and hypercholesterolemia that not control with one drug or high LDL-C and low HDL-C. The use of niacin and statin are very helpful for patient with LDL-C that not controlled by statin and HDL-C is below 40 mg/dl. Patient with hyperlipidemia (hypertriglyceridemia and hypercholesterolemia) that treated by fibrate do not reach normal LDL-C level and this patients are candidate for statin added to their treatment that can slightly increase HDL-C Downloaded from ijdo.ssu.ac.ir at 1:45 IRST on Saturday November 7th 2020 level (5 -10%), although fibrate effect on HDL-C (increase 5 -10%) but niacin is more effective for increase of HDL-C (30%) (33).

Conclusions
There were statistical significance decrease of TG, LDL-C and total cholesterol and increase of HDL-C in both groups. There were significant changes in HDL and TG in group B than group A. There were no any drug complication in two groups.