Glycated Hemoglobin and Serum Lipid Profile Associations in Type 2 Diabetes Mellitus Patients

V Siva Prabodh et al. / JPBMS, 2012, 17 (12)

Available online at www.jpbms.info ISSN NO- 2230 – 7885 OriginalJPBMS article CODEN JPBSCT

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL SCIENCES

Samatha P1, *Siva Prabodh V2, Chowdary NVS2, Ravi Shekhar2

1MSC , 2 MD, Dept. of Biochemistry, NRI Medical College and Hospital, Chinakakani, A.P- 522503, India.

Abstract: Diabetic patients with accompanied (but often unnoticed) dyslipidemia are soft targets of cardiovascular deaths. An early intervention to normalize circulating lipids shown to reduce cardiovascular complications and mortality. Glycated hemoglobin (HbA1c) is a routinely used marker for long – term glycemic control. This investigation is an attempt to evaluate the association between HbA1c and various lipid parameters. Venous blood samples collected from 50 type 2 diabetic patients (26 males, 24 females) and serum analyzed for HbA1c, Fasting blood glucose, Total Cholesterol, Triacylglycerols, HDL-C and LDL-C. L/H risk ratio is also calculated. The levels of HbA1c (%) did not differ significantly between males (8.51 ± 1.17) and females (8.24 ± 1.89), whereas male patients had higher mean values of FBG and various lipid parameters than in females. Patients with HbA1c value >7.0 % showed direct and significant correlation with FBG, TC, LDL-C, L/H risk ratio as compared to patients with HbA1c ≤ 7.0%. There was no significant difference in TG, HDL-C between two groups of glycated hemoglobin. These findings indicate that HbA1c is utilized for screening high risk diabetic patients for early diagnosis of dyslipidemia and timely intervention with lipid lowering drugs.

Keywords: Diabetes, Dyslipidemia, Glycated hemoglobin, Association.

Introduction: importance of HbA1c as an indicator of dyslipidemia in Diabetes is a global endemic with rapidly increasing type 2 diabetic patients. prevalence in both developing and developed countries [1]. The International Diabetes Federation (IDF) reported that Materials and methods: total number of diabetic subjects in India is 41 million in The study comprised of a total of fifty Type 2 diabetic 2006 and that this would raise to 70 million by the year patients (26 males and 24 females) who visited the 2025 [2]. Studies on migrant Indians have shown that they Outpatient department of NRI general Hospital, have a higher predisposition to insulin resistance, type 2 Chinakakani, Guntur district, Andhra Pradesh. Ethical diabetes and coronary artery disease compared to other clearance obtained for the study from the hospital. Venous ethnic groups [3]. There is a higher risk of cardiovascular blood samples collected from all the patients after at least disease in people with type 2 diabetes, while 10 hours fasting into centrifuge tubes. The blood allowed cardiovascular deaths represent the top killer in this to clot and then centrifuged at 3000 rpm for 15 min at population [4]. Epidemiological studies have demonstrated room temperature. The serum analyzed for total that diabetes mellitus is an independent risk factor for cholesterol by enzymatic (CHOD-PAP) colorimetric method cardiovascular disease and it amplifies the effects of other [10] and triglycerides by enzymatic (GPO-PAP) method [11]. common risk factors such as smoking, hypertension and HDL-Cholesterol estimated by precipitant method [12] and dyslipidemia [5]. Hyperlipidemia is one of the most risk LDL-Cholesterol by Friedewald formula [13] as shown factors for coronary artery disease (CAD) which is more below. prevalent among adults with type 2 diabetes mellitus than in the general population with a four to six fold greater LDL-C = TC - HDL-C – (TG/5). cardiovascular mortality [7]. Glycated Hemoglobin (HbA1c) The serum glucose determined by using the glucose is a routinely used marker for long term glycemic control. oxidase enzymatic method [14]. All the parameters under HbA1c predicts the risk for develop diabetic complications investigation were determined in the serum of the subjects in diabetic patients. Now-a-days, elevated levels of HbA1c using commercially available reagent kits.HbA1c estimated have been regarded as an independent risk factor for by using Ion exchange chromatography (Crest A Coral cardiovascular disease in subjects with or without Clinical system, USA). For serum lipid reference level diabetes. Each one percent increase in absolute HbA1c National Cholesterol Education Programme (NCEP) Adult shows eighteen percent increase for cardiovascular disease Treatment Panel III (ATP III) guideline was referred. [8]. Positive relationship between HbA1c and According to NCEP ATP III guideline hypercholesterolemia cardiovascular disease shown in non diabetic cases even defined as TC > 200 mg/dl, high LDL-C when value > 100 within normal range of HbA1c [9]. This study was mg/dl, hypertriglyceridemia > 150 mg/dl and low HDL-C conducted to know the relationship between glycemic when value < 40 mg/dl. Dyslipidemia defined by presence control and serum lipid profile and evaluated the of one or more than one abnormal serum lipid

1 Journal of Pharmaceutical and Biomedical Sciences© (JPBMS), Vol. 17, Issue 17 V Siva Prabodh et al. / JPBMS, 2012, 17 (12) concentration. Values of HbA1c were given as % of total hemoglobin and values of all other parameters were given in mg/dl. All values were expressed as mean ± SD. Independent samples t test (2 tailed) was used to compare means of different parameters. Pearson’s correlation test performed to examine various correlations.

Results: Fifty Type 2 diabetic subjects included in the study out of which 26 were males and 24 were females. The mean age ± SD of male and female subjects were 58.56 ± 9.28 and 52.48 ± 14.06 years respectively. The mean value of HbA1c and FBG were higher in males in comparison to female subjects but the differences were non significant. Among circulating lipids the mean values of total cholesterol, triacylglycerols, LDL-C, HDL-C were higher in males than (b) Positive Correlation between HbA1c and Total cholesterol. female patients. These differences were statistically non Statistically significant (r=0.309). significant (Table 1).

Table 1: Lipid Profile Parameters between Male and Female Type 2 Diabetic Patients. Parameters Males (n=26) Females (n=24) t table Mean ± SD Mean ± SD value Fasting Blood 168.50 ± 69.42 156.00 ± 66.25 0.65 Glucose Total 186.19 ± 52.28 173.46 ± 41.74 0.95 Cholesterol Triacylglycerols 174.38 ± 112.14 143.50 ± 56.51 1.22 HDL-C 39.35 ± 8.53 38.42 ± 7.46 0.41 LDL-C 111.97 ± 85.20 106.34 ± 75.38 0.57 HbA1c 8.52 ± 1.18 8.25 ± 1.90 0.61 HDL-C = high density lipoprotein – cholesterol, LDL-C = low density lipoprotein – cholesterol Hypercholesterolemia was found in 26 (52%) subjects, (c) Positive Correlation between HbA1c and Triglycerides. similarly hypertriglyceridemia was found in 24 (48%), Statistically non significant (r=0.189). decreased HDL-C was found in 33 (66%) and increased LDL-C was found in 30 (60%) subjects. Thirty six (72%) subjects had only one abnormal lipid profile parameter, 28 (56%) had two abnormal lipid parameter, 11 (22%) had more than two abnormal lipid profile parameter. According to NCEP ATP III guidelines, 15 (58%) males out of 26 and 16 (67%) females out of 24 were dyslipidemic. Highly significant correlation observed between FBG and HbA1c (r=0.338). HbA1c also demonstrated direct and significant correlation with TC (r=0.309), LDL-C (r=0.306). The correlation between HbA1c with TG (r=0.189) and HDL-C (r=0.104) was slightly positive, and it was statistically non significant (figure 1).

Figure 1: Correlations between HbA1c, FBG and Lipid Profile Parameters (d) Positive Correlation between HbA1c and HDL. Statistically not significant (r=0.104).

(a) Positive Correlation between HbA1c and FBG. Statistically Highly significant(r=0.338). (e) Positive Correlation between HbA1c and LDL-Cholesterol. Statistically significant (r=0.306).

2 Journal of Pharmaceutical and Biomedical Sciences© (JPBMS), Vol. 17, Issue 17 V Siva Prabodh et al. / JPBMS, 2012, 17 (12) gylcemic control. The level of HbA1c value ≤ 7.0 % was said to be appropriate for reducing the risk for cardiovascular complications [22]. In the present study, diabetic patients were divided into two groups as per the cutoff of 7.0 %. The diabetic patients with HbA1c value > 7.0 % showed increased mean values of TC, TG, LDL / HDL-C ratio and risk ratio; but it was statistically non significant in comparison to patients with HbA1c value ≤ 7.0 %. Khan et et al. [23] reported the impact of glycemic control on various lipid parameters and observed the significant alterations in all lipid parameters except LDL-C with regard to glycemic control. The severity of dyslipidemia increases in patients with higher HbA1c value. Elevated levels of HbA1c and dyslipidemia are independent risk factors of cardiovascular diseases and hence, diabetic patients with (f) Positive Correlation between HbA1c and LDL/HDL ratio . elevated HbA1c and dyslipidemia considered as high risk Statistically not significant (r=0.146). group for cardiovascular disease. Improving glycemic Table 2 shows classification of subjects into two groups as control can reduce the risk of cardiovascular events in [24] per their glycemic index. First group consists of patients diabetes . The present study shows significant with HbA1c value ≤ 7.0% and second group with HbA1c correlation between HbA1c and various lipid parameters, value > 7.0%. The mean values of TC, TG, LDL-C, LDL- higher mean values of lipid parameters and significant risk C/HDL-C and L/H risk ratio were high in patients with ratio between two groups (≤ 7.0 %. and > 7.0%) of glycated HbA1c value > 7.0%. FBG was significantly higher in hemoglobin indicating that HbA1c is utilized for screening second group when compared to first group. high risk diabetic patients for early diagnosis of dyslipidemia and timely intervention with lipid lowering Table 2: Biochemical Parameters categorized by patient’s glycemic drugs. control (HbA1c) Parameters Glycated Hemoglobin (HbA1c) t table References: ≤ 7.0 % (n =20) > 7.0 % (n = 30) value Mean ± SD Mean ± SD 1.Berry C, Tardif J C, Bourassa M G. Coronary heart disease Total Cholesterol (TC) 174.30 ± 49.15 183.93 ± 46.72 0.80 in patients with diabetes: part I: recent advances in Triacylglycerols 147.20 ± 70.03 167.80 ± 102.03 0.82 prevention and noninvasive management. J.Am.Coll.Cardiol HDL-C 38.30 ± 9.52 39.30 ± 6.86 0.59 2007; 49:631-42. LDL-C 29.44 ± 14.01 33.56 ± 20.41 0.81 2.Sicree R, Shaw J, Zimmet P. Diabetes and impaired Risk ratio (TC / HDL-C) 0.77 ± 0.30 0.86 ± 0.52 0.68 glucose tolerance. In: Gan D, editor. Diabetes Atlas. LDL-C / HDL-C 2.83 ± 1.89 2.88 ± 2.08 0.20 International Diabetes Federation. 3rd ed. Belgium: Fasting Blood Glucose 133.75 ± 43.17 181.67 ± 74.78 2.78** International Diabetes Federation 2006; p.15-103.

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Conflict of Interest:- None Source of finding:- Not declared.

Quick Response code (QR-Code) Corresponding Author:- for mobile user to access JPBMS V. Siva Prabodh., website electronically. Website link:- www.jpbms.info Associate Professor, Dept. of Biochemistry, NRI Medical College and Hospital, Chinakakani, A.P-522503, India. Contact no:-+91-9849231126