Association of Hypothyroidism with High Non-HDL Cholesterol and Ankle Brachial Pressure Index in Patients with Diabetes: 10-Year Results from a 5780 Patient Cohort. A Need for Intervention

Research Article

Annals Thyroid Res. 2016; 2(2): 53-57.

Association of Hypothyroidism with High Non-HDL Cholesterol and Ankle Brachial Pressure Index in Patients with Diabetes: 10-Year Results from a 5780 Patient Cohort. A Need for Intervention

Kamran MA Aziz*

Diabetologist, Aseer Diabetes Center, Aseer Central Hospital, Saudi Arabia

*Corresponding author: Kamran Mahmood Ahmed Aziz, Research scientist (Diabetes, Endocrinology and Metabolism) Diabetology Clinic, Aseer Diabetes Center of Aseer Central Hospital, Ministry of Health, P. O. Box 34, Abha, Saudi Arabia

Received: May 17, 2016; Accepted: June 17, 2016; Published: June 21, 2016


Diabetes is commonly associated with thyroid gland disorders, especially hypothyroidism. Among diabetic subjects with hypothyroidism there is a need to study biochemical and other parameters for risk of cardiovascular and kidney diseases. In the past, no study was conducted which has demonstrated significant associations of non-HDL-cholesterol and Ankle Brachial Index (ABI) in such patients. This was accomplished in the current study which has recruited a cohort of 5780 diabetic patients with hypothyroidism, during more than 10-years of follow up, with a hypothesis that hypothyroidism could be associated with higher non-HDL-C and ABI measurements. Statistical analysis of this research has demonstrated that subjects with hypothyroidism have significantly higher levels of non-HDL-C as compared to those without hypothyroidism (153 ± 42.7; 95% CI 146.6 to 158.8 verses148 ± 40; 95% CI 142.5 to 151.6; p < 0.001). Right foot ABI was higher among diabetics with hypothyroidism (1.34 ± 0.387; 95% CI 1.19 to 1.56 versus 1.23 ± 0.314; 95% CI 1.12 to 1.26; p < 0.001), as well as for the left foot ABI (1.32 ± 0.375; 95% CI 1.23 to 1.54 versus 1.23 ± 0.371; 95% CI 1.12 to 1.28).

Higher levels of non-DHL-C and ABI are associated with cardiovascular and diabetic kidney disease risk and progression. These conditions when associated with hypothyroidism, carry a higher risk of mortality and morbidity. Hence early intervention and screening is required for diabetic subjects for hypothyroidism, dyslipidemia and ABI for lower limbs, to prevent further complications.

Keywords: Hypothyroidism; Dyslipidemia; Diabetic; CKD


Thyroid gland disorders or dysfunctions are associated with changes in insulin sensitivity, insulin resistance and impaired glycemic control [1]. Regarding non diabetic and general population, subclinical hypothyroidism occurs in 5–15% among them and may be a risk factor for the development aortic atherosclerosis and myocardial infarction [2-4]. This has been attributed to several mechanisms, including diastolic blood pressure and dyslipidemia. Additionally, research trials have shown that they have a higher Intima-Media Thickness (IMT) of the carotid artery with left ventricular systolic dysfunction, which worsens during effort and a risk for myocardial infarction; these patho-physiological changes can be reversed with Thyroxine Replacement Therapy (TRT) [5-9].

Hypothyroidism is also significantly associated with altered lipoprotein metabolism and dyslipidemia, i.e., a higher total cholesterol, LDL-C (low density lipoprotein cholesterol) and triglycerides, which in turn is a risk factor for Coronary Heart Disease (CAD) and Chronic Kidney Disease (CKD) [10-15]. Additionally, HDL-Cholesterol (HDL-C) is considered as a good cholesterol (as compared to LDL cholesterol and triglycerides, which are considered as bad cholesterol and CAD risk factors). Conversely, non-HDL-C can be derived simply by abstracting HDL-C from total cholesterol, which will give a better index of overall bad cholesterol, a risk for CAD. Recently importance of non-HDL cholesterol as a potential secondary marker of dyslipidemia and CAD risk factor has emerged [16,17]. Previous research trials have not measured non-HDL in hypothyroid diabetic subjects, which calls to conduct such research trial.

Furthermore, extensive research has shown that not only a low ABI (= 0.9) is a predictor of Cardiovascular Diseases (CVD), but an abnormally elevated ABI is also associated with high CVD risk [18- 24]. Furthermore, it has been demonstrated that subjects with high ABI have poor prognosis or survival, as compared to those with a normal ABI or low ABI [25]. Similarly, Patients with Type 2 Diabetes Mellitus (T2DM) are at higher risk of developing macrovascular disease, especially CAD, cerebrovascular disease, and PAD. A high ABI can be utilized as a simple screening diagnostic test for such patients and a prognostic indicator for CVD and PVD. However, its direct association with hypothyroidism needs to be studied in depth.

Under this research background, the aim of current study was to measure non-HDL cholesterol and ABI among diabetic hypothyroid subjects and to study their significant associations, which until date has not been studied.

Materials and Methods

Laboratory samples collection, and data retrieval

Current study is a prospective, cross sectional and observational cohort study. Present study included the diabetic patients who were on routine follow up in diabetology clinic of Aseer Diabetes Center and referred from primary health care centers to tertiary care diabetic center for routine evaluations and follow up. Study included known type-1 and type-2 diabetic patients. Children (age <13 years), pregnant diabetic subjects, and patients on End Stage Renal Disease (ESRD) or on dialysis and with active hepatic disease were excluded from the study. Data were collected for more than 10 years (10 years and 6 month), from August 2005 to February 2016.

Detailed history was taken and physical examination was done to complete assessments. Diabetic patients, who were recently diagnosed (within 3-4 months) with subclinical or clinical hypothyroidism by endocrinology department, and following regularly with diabetologist for diabetes management, were also selected. These patients were labeled as “Hypothyroidism “. Blood pressure, weight and height were measured by standardized methodology. Body Mass Index (BMI) was measured by the formula, weight (kg)/height (m²). BMI = 30 kg/m² was labeled as obesity.

All laboratory measurements were done in fasting state, early in the morning of not less than 12 hours, and were sent to Aseer Central Hospital laboratory.

HDL-C (mg/dl) was measured in plasma by Automated High Density Lipoprotein (AHDL) method by the Dimension® clinical chemistry system and analyzer (Siemens healthcare diagnostics Inc. Newark, DE 19714, U.S.A), an in vitro diagnostic test intended for quantitative determination of High Density Lipoprotein Cholesterol (HDL-C). Total cholesterol was measured directly by CHOL method (based on enzymatic procedures), a quantitative determination by the Dimension® clinical chemistry system and analyzer. Then their difference were calculated for the measurement of non-HDLCholesterol (i.e., non-HDL-C = total cholesterol – HDL-C).

Ankle Brachial Index (ABI) was measured by a standardized doppler ultrasonic device or arterial doppler, atys Mèdical Doppler System Inc. USA (approved by FDA). Measurements were carried out on the patients after a 5-minute rest in the supine position. First, Doppler probe (8 MHz) was used to measure brachial pressure in right arm. Then same procedure was applied to right foot pressure (dorsalis pedis or posterior tibial artery, whichever was higher). Right ABI was calculated as the ratio of the two pressures (i.e., ABI = brachial pressure / foot pressure). Same procedure was repeated to measure for the right side of arm and foot (left ABI).

All sample requests were entered and retrieved by central computerized network, Natcom Hospital Information System (NATCOM HIS; National Computer System Co. Ltd) [26], a server based hospital management information system interconnecting all departments of Aseer Central Hospital and its diabetes center.

This study was reviewed and approved by the research committee of Aseer Diabetes Center; consent was taken from the participating patients and all methodologies on subjects reported in current study were in accordance with Helsinki Declaration of 1975 (revised in 2008).

Statistical methods

Variables of interest were entered, and all data were analyzed using IBM® SPSS® Statistics version 20 for Windows (SPSS®Inc, USA). All statistical tests were performed by standardized bio-statistical methodologies. Student’s t test was utilized to measure significant difference for the variables among groups (with and without hypothyroidism).

This study was designed to have a statistical power of 90% to detect significant changes. All p-values were two-sided, and p-values less than 0.05 were considered statistically significant.


Data for 5780 patients were analyzed for the significant results. There were 3699 (64%) males and 2081 (36%) females in the study with 815 (14%) type-1 and 4965 (86%) type-2 subjects. Obesity was found in 2427 (42%); 1390 (24%) were hypothyroid and were on TRT. These demographic data is presented in Table 1. Data for univariate descriptive statistics is shown in Table 2.