OBJECTIVE

Reduction of atherosclerotic cardiovascular disease (ASCVD) risk in patients with diabetes requires proper management of lipid parameters. This study aimed to find the pattern of dyslipidemia and scope of ASCVD risk reduction in patients with diabetes by lipid management.

METHODS

Clinical, biochemical, and medication profiles of all patients with diabetes attending a tertiary diabetes care hospital over a 2-year period were collected. The prevalence of various lipid abnormalities was determined after excluding patients with thyroid dysfunction and those on lipid-lowering medications. Patients were stratified according to LDL cholesterol, HDL cholesterol, and triglyceride levels, and other clinical parameters were compared among the groups. The adequacy of statin treatment was assessed based on American Diabetes Association guidelines.

RESULTS

Nine hundred and seventy-one patients were included. The prevalence of hyperlipidemia was 40.0%, of whom 14.6% were newly diagnosed. The most common lipid abnormality was elevated LDL cholesterol. Higher A1C and fasting blood glucose values were found to be associated with higher LDL cholesterol levels. Twenty-seven percent of patients with indications for treatment with statins were receiving them. Of those being treated with statins, 42.6% had an LDL cholesterol level ≥100 mg/dL.

CONCLUSION

In South Indian patients with type 2 diabetes and fair glycemic control, high LDL cholesterol is the predominant lipid abnormality. There remains a huge potential for ASCVD risk reduction in this population if the knowledge practice gap is addressed.

Type 2 diabetes requires proper management of lipid parameters and hypertension in addition to glycemic control to ensure prevention of chronic complications, especially negative macrovascular outcomes. The prevalence of macrovascular complications of diabetes is much higher in Indians than in Caucasians, even though the prevalence of microvascular complications is comparable in these populations (1,2).

Only a few studies of lipid parameters in Indian patients with diabetes have been conducted. This knowledge deficit is particularly worrisome with regard to the population of South India, and especially in the state of Kerala, where the predicted risk of atherosclerotic cardiovascular disease (ASCVD) is the highest among the Indian states, with an age-standardized state-level mean 10-year ASCVD risk of 30.4% among males (3). The prevalence of dyslipidemia among people ≥30 years of age in South India is 74.8% in urban populations (4).

International guidelines on the treatment of dyslipidemia in patients with type 2 diabetes advocate aggressive lowering of LDL cholesterol in patients with diabetes based on strong evidence from clinical trials. Therapeutic inertia with regard to glucose, blood pressure, and lipid management in patients with diabetes has been demonstrated in multiple studies around the world (5,6). This study assesses the prevalence and pattern of dyslipidemia, as well as the adequacy of its management, at a tertiary care center in South India.

This study was conducted at the Indian Institute of Diabetes in Thiruvananthapuram, India, which is a tertiary referral diabetes care center. The study was approved by the Human Ethics Committee at Government Medical College in Thiruvananthapuram.

Data collection from the Indian Institute of Diabetes was permitted by the director of the Institute. The data were obtained from electronic records of the clinical, biochemical, and medication profiles of all patients attending the hospital during the 2-year study period. Anthropometric measurements were taken by trained staff, and clinical details, diagnoses, and medications were recorded into the electronic database by the treating physicians. Biochemical reports were entered into electronic records directly from the laboratory. Trained staff members completed separate forms for each patient, by retrieving the patient’s electronic records.

Subjects included all consecutive patients aged 18–85 years with type 2 diabetes who were attending the hospital (for the first time or for follow-up) who had a lipid profile and an A1C during the study period from August 2014 to December 2016. Patients with subclinical or overt hypothyroidism, severe anemia (hemoglobin ≤7 g/dL), chronic liver disease of alcoholic or nonalcoholic etiology, alcohol dependence, chronic kidney disease on dialysis, pregnancy, or lactation were excluded from the study.

Demographic parameters, duration of diabetes, anthropometric measurements, and blood pressure were noted from patients’ last visit records. History of addictions and comorbidities was also noted from records. Laboratory data were collected from patients’ last visit records and included A1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG), fasting lipid profile, thyroid profile, renal function test results, and hemogram. All biochemical investigations were performed using the same analyzers under a National Accreditation Board for Laboratories–certified quality control program (7). Plasma glucose estimation was done with the glucose oxidase method, and lipid parameters, serum creatinine (Cr), aspartate transaminase (AST), alanine transaminase (ALT), and serum uric acid were assessed using an auto-analyzer (ERBA 360, ERBA Mannheim, Mumbai, India). A1C was estimated using a National Glucose Standardization Program–certified high-performance liquid chromatography system (BIORAD-D10, Bio-Rad Laboratories, Hercules, CA). Urine microalbumin was estimated from a nonfasting second-voided urine sample with the nephelometric method (MISPA I2, Agappe Diagnostics, Cham, Switzerland). Hemogram was estimated using the Mindray-BC3000 plus cell counter (China), and erythrocyte sedimentation rate (ESR) was estimated using the Westergren tube method. Thyroid-stimulating hormone (TSH) level was assessed using Eclysys 2000 electro-chemiluminiscence system with commercially available kits (Roche, Germany). From the available parameters, BMI and estimated glomerular filtration rate (eGFR; Cockcroft and Gault method) were calculated for each patient.

Patients were identified as having hyperlipidemia if the previous treatment records mentioned it in the diagnosis, if serum total cholesterol was ≥250 mg/dL, or if LDL cholesterol was ≥150 mg/dL in people who were not taking cholesterol-lowering therapy. Low HDL was defined as <40 mg/dL for males and <50 mg/dL for females. Hypertriglyceridemia was determined to be present if the serum triglyceride (TG) level was ≥250 mg/dL. Dyslipidemia was defined as the presence of any of these lipid abnormalities (i.e., previous record mentioning it in the diagnosis, total cholesterol ≥250 mg/dL, LDL cholesterol ≥150 mg/dL, low HDL cholesterol, or hypertriglyceridemia).

Cardiovascular risk parameters such as duration of diabetes, A1C, systolic and diastolic blood pressure, eGFR, and other clinical metrics such as hemoglobin levels and ESR were dichotomized based on the cutoff values mentioned in Table 1. Waist-to-hip ratios of >0.85 and >0.9 were considered to indicate abdominal obesity in females and males, respectively. Prevalence rates were determined for previously diagnosed and newly diagnosed hyperlipidemia. The prevalence of statin prescription was assessed in the study population. The number of patients with an indication for starting statin therapy according to the American Diabetes Association (ADA) (8) recommendations was also assessed.

TABLE 1

Baseline Characteristics of Subjects (Continuous Variables)

Age, years 53.1 ± 11.1 
Duration of diabetes, years 9.4 ± 7.7 
BMI, kg/m2 26.8 ± 3.9 
Systolic blood pressure, mmHg 131.1 ± 18.4 
Diastolic blood pressure, mmHg 77.3 ± 8.9 
Waist-to-hip ratio 0.98 ± 0.10 
Hemoglobin, g/dL 13.4 ± 1.6 
Total leukocyte count 1,658 ± 2,418 
ESR, mm/hour 13.00 ± 6.23 
Serum Cr, mg/dL 1.00 ± 0.54 
eGFR, mL/min/1.73 m2 89.7 ± 47.3 
TSH, mIU/mL 2.15 ± 1.00 
AST, IU/mL 31.0 ± 22.6 
ALT, IU/mL 40.47 ± 32.30 
Total cholesterol, mg/dL 184.7 ± 44.3 
Triglycerides, mg/dL 135.5 ± 81.9 
HDL cholesterol, mg/dL 46.18 ± 14.80 
LDL cholesterol, mg/dL 111.3 ± 39.8 
A1C, % 8.61 ± 2.30 
FPG, mg/dL 179.65 ± 72.20 
Serum uric acid, mg/dL 4.81 ± 1.45 
Age, years 53.1 ± 11.1 
Duration of diabetes, years 9.4 ± 7.7 
BMI, kg/m2 26.8 ± 3.9 
Systolic blood pressure, mmHg 131.1 ± 18.4 
Diastolic blood pressure, mmHg 77.3 ± 8.9 
Waist-to-hip ratio 0.98 ± 0.10 
Hemoglobin, g/dL 13.4 ± 1.6 
Total leukocyte count 1,658 ± 2,418 
ESR, mm/hour 13.00 ± 6.23 
Serum Cr, mg/dL 1.00 ± 0.54 
eGFR, mL/min/1.73 m2 89.7 ± 47.3 
TSH, mIU/mL 2.15 ± 1.00 
AST, IU/mL 31.0 ± 22.6 
ALT, IU/mL 40.47 ± 32.30 
Total cholesterol, mg/dL 184.7 ± 44.3 
Triglycerides, mg/dL 135.5 ± 81.9 
HDL cholesterol, mg/dL 46.18 ± 14.80 
LDL cholesterol, mg/dL 111.3 ± 39.8 
A1C, % 8.61 ± 2.30 
FPG, mg/dL 179.65 ± 72.20 
Serum uric acid, mg/dL 4.81 ± 1.45 

Data are mean ± SD.

Data were tabulated in Excel 2010 (Microsoft, Redmond, WA), and statistical analyses were performed with SPSS Statistics version 25 (IBM Corp., Armonk, NY). Continuous variables were expressed as mean ± SD, and categorical variables were expressed as frequencies and percentages. The variables were tested for their distribution and classified as normally distributed or not. Student t tests and one-way ANOVA were used for continuous variables. χ2 and Fischer’s exact tests were used for categorical variables as appropriate for determining the strengths of association. P <0.05 was considered significant.

A total of 1,152 patients with diabetes who had undergone a fasting lipid profile, A1C, and serum TSH testing during a single clinic visit were enrolled in the study. Of these, 181 patients had clinical or subclinical hypothyroidism and were excluded, and the details on these patients were published elsewhere (7). The remaining 971 patients were included in the final analyses.

Baseline demographic, clinical, and biochemical parameters of the study population are provided in Tables 1 and 2. Patients’ mean age was 53.1 ± 11.1 years and mean duration of diabetes was 9.4 ± 7.7 years, and 67.7% were male. The mean baseline A1C was 8.6 ± 2.3%.  Two hundred and thirty-two patients (23.9%) had anemia, defined as a hemoglobin level of ≤13 g/dL for males and ≤12 g/dL for females. Only 28 patients (2.9%) had a hemoglobin level ≤10 g/dL.

TABLE 2

Baseline Characteristics of Subjects (Categorical Variables)

Male sex 658 (67.7) 
Smokers* 77 (7.9) 
Alcoholism* 166 (17.1) 
Hypertension 289 (29.8) 
Obese (BMI ≥27 kg/m2390 (40.2) 
Overweight (BMI ≥23 kg/m2381 (39.2) 
Systolic blood pressure ≥140 mmHg 328 (33.8) 
Diastolic blood pressure ≥90 mmHg 126 (13.0) 
Anemia (hemoglobin ≤13 g/dL for males and ≤12 g/dL for females) 232 (23.9) 
ESR ≥20 mm/hour 311 (32) 
eGFR <60 mL/min/1.73 m2 155 (16) 
Serum Cr ≥1.2 mg/dL 142 (14.6) 
Urine albumin-to-creatinine ratio ≥30 mg/g Cr 280 (28.8) 
Uric acid ≥5 mg/dL 391 (40.2) 
A1C ≥7% 605 (62.3) 
Male sex 658 (67.7) 
Smokers* 77 (7.9) 
Alcoholism* 166 (17.1) 
Hypertension 289 (29.8) 
Obese (BMI ≥27 kg/m2390 (40.2) 
Overweight (BMI ≥23 kg/m2381 (39.2) 
Systolic blood pressure ≥140 mmHg 328 (33.8) 
Diastolic blood pressure ≥90 mmHg 126 (13.0) 
Anemia (hemoglobin ≤13 g/dL for males and ≤12 g/dL for females) 232 (23.9) 
ESR ≥20 mm/hour 311 (32) 
eGFR <60 mL/min/1.73 m2 155 (16) 
Serum Cr ≥1.2 mg/dL 142 (14.6) 
Urine albumin-to-creatinine ratio ≥30 mg/g Cr 280 (28.8) 
Uric acid ≥5 mg/dL 391 (40.2) 
A1C ≥7% 605 (62.3) 

Data are n (%).

*

Patients with a history of alcohol intake or smoking anytime in their life.

Patients with a previous diagnosis of hypertension.

Prevalence of Hyperlipidemia

The prevalence of previously diagnosed hyperlipidemia was 25.6% (249 of 971 patients), whereas another 14.6% of cases of hyperlipidemia (142) were newly found based on a high total cholesterol (≥250 mg/dL) or a high LDL cholesterol (≥150 mg/dL) level. Thus, the total prevalence of hyperlipidemia (previously diagnosed plus newly diagnosed) was 40.2%.

Pattern of Dyslipidemia

The lipid profiles of patients not taking statins (n = 708) was assessed (Figure 1). High LDL cholesterol based on a cutoff value of 150 mg/dL was present in 119 of these patients (16.8%). Analysis was also performed to determine the proportion of patients with an LDL cholesterol level ≥100 mg/dL, and ≥70 mg/dL as a risk factor for ASCVD in patients with diabetes. Four hundred patients (56.5%) and 817 patients (84.1%) had an LDL cholesterol level ≥100 and ≥70 mg/dL, respectively. A TG level ≥250 mg/dL was found in 53 patients (7.49%), whereas 207 patients (29.4%) had a TG level ≥150 mg/dL. Low HDL cholesterol (<40 mg/dL in males and <50 mg/dL in females) was seen in 303 patients (42.7%). Thus, LDL cholesterol elevated above the ADA ASCVD risk cutoff value for patients with diabetes and low HDL cholesterol were the two most prevalent lipid profile abnormalities in this population.

FIGURE 1

Comparison of mean TG, LDL cholesterol, and HDL cholesterol levels from this and similar studies.

FIGURE 1

Comparison of mean TG, LDL cholesterol, and HDL cholesterol levels from this and similar studies.

Close modal

Factors Associated With Different Lipoprotein Fractions

Among patients not taking a statin, a comparison was made between those with an LDL cholesterol level ≥150 mg/dL and those with a level <150 mg/dL and to find the clinical associations of high LDL level (Table 3). Increased ESR and higher A1C, FPG, and PPG levels were found to be associated with higher LDL cholesterol levels. Similar comparisons were done for TG and HDL cholesterol levels. High TG levels (≥250 mg/dL) were associated with lower duration of diabetes and higher diastolic blood pressure, A1C, FPG, PPG, AST, ALT, and total leukocyte count. Rise in blood glucose after a meal also showed an association with serum TG level. Low HDL cholesterol (<40 mg/dL in males and <50 mg/dL in females) was found to be associated with lower age, lower hemoglobin levels, and elevated ESR. Serum uric acid levels were found to be significantly elevated in those with TG levels ≥250 mg/dL. The group with TG ≥250 mg/dL and LDL cholesterol ≥150 mg/dL were significantly younger than the group with lower TG and LDL cholesterol levels.

TABLE 3

Comparison Among Statin-Naive Patients Based on LDL Cholesterol, Triglyceride, and HDL Cholesterol Levels

ParameterLDL Cholesterol, mg/dLPTriglycerides, mg/dLPHDL Cholesterol, mg/dLP
>150 (n = 119)<150 (n = 589)>250 (n = 53)<250 (n = 651)Low(n = 303)Normal (n = 401)
Age, years 47.71 ± 10.91 52.98 ± 11.59 <0.001* 46.04 ± 10.82 52.59 ± 11.58 <0.01* 51.11 ± 12.08 52.78 ± 11.21 0.05 
Diabetes duration, years 7.66 ± 7.20 9.00 ± 7.60 0.126 5.77 ± 6.38 9.04 ± 7.60 0.01* 7.93 ± 7.09 9.28 ± 7.69 0.18 
BMI, kg/m2 26.42 ± 3.63 26.35 ± 3.84 0.842 25.62 ± 3.77 26.42 ± 3.81 0.15* 26.50 ± 3.72 26.25 ± 3.88 0.22 
Systolic blood pressure, mmHg 130.38 ± 22.30 130.45 ± 17.42 0.973 129.86 ± 21.66 130.48 ± 18.03 0.82 129.18 ± 18.62 131.30 ± 18.03 0.84 
Diastolic blood pressure, mmHg 77.48 ± 9.40 77.60 ± 9.12 0.892 80.43 ± 10.22 77.36 ± 9.04 0.02* 77.47 ± 9.19 77.62 ± 9.14 0.76 
Waist-to-hip ratio 0.98 ± 0.05 0.98 ± 0.11 0.555 0.99 ± 0.05 0.98 ± 0.11 0.26 0.97 ± 0.09 0.97 ± 0.11 0.88 
Hemoglobin, g/dL 13.49 ± 1.63 13.44 ± 1.63 0.731 14.44 ± 1.76 13.37 ± 1.59 <0.01* 13.21 ± 1.78 13.62 ± 1.48 0.005* 
Total leukocyte count, cells/mm3 6,710.00 ± 1,919.53 6,627.69 ± 1,509.83 0.606 7,062.26 ± 1,810.46 6,607.36 ± 1,562.12 0.04* 6,774.25 ± 1,652.47 6,531.27 ± 1,515.21 0.74 
ESR, mm/hour 20.17 ± 19.11 17.02 ± 15.64 0.05 18.98 ± 21.69 17.44 ± 15.83 0.52 19.81 ± 18.29 15.85 ± 14.45 <0.01* 
Cr, mg/dL 1.04 ± 0.69 0.98 ± 0.45 0.255 1.06 ± 0.70 0.99 ± 0.48 0.34 0.99 ± 0.69 0.98 ± 0.27 0.01* 
eGFR, mL/min/1.73 m2 90.87 ± 31.21 91.84 ± 55.15 0.856 100.48 ± 36.90 90.97 ± 52.93 0.20 94.68 ± 60.61 89.23 ± 44.21 0.23 
Urine albumin-to-creatinine ratio, mg/g Cr 60.54 ± 95.29 45.06 ± 75.39 0.052 47.92 ± 68.67 47.68 ± 80.13 0.98 41.04 ± 68.36 52.96 ± 86.54 <0.01* 
TSH, μIU/ml 2.28 ± 1.13 2.15 ± 1.03 0.208 2.19 ± 1.06 2.17 ± 1.04 0.88 2.19 ± 1.04 2.14 ± 1.03 0.98 
AST, IU/L 33.43 ± 48.99 31.84 ± 17.38 0.538 42.38 ± 71.90 31.28 ± 16.87 <0.01* 31.41 ± 18.51 32.57 ± 29.82 0.29 
ALT, IU/L 43.45 ± 49.21 40.35 ± 31.07 0.375 53.30 ± 64.93 39.87 ± 30.94 0.01* 40.09 ± 29.47 41.33 ± 38.34 0.05 
A1C, % 9.13 ± 2.79 8.49 ± 2.27 0.007* 9.34 ± 2.39 8.54 ± 2.37 0.02* 8.59 ± 2.26 8.59 ± 2.46 0.28 
FPG, mg/dL 200.30 ± 88.43 176.38 ± 70.49 0.001* 215.02 ± 87.09 177.61 ± 72.52 < 0.01* 179.94 ± 70.99 180.59 ± 76.79 0.31 
Uric acid, mg/dL 4.83 ± 1.75 4.77 ± 1.40 0.679 5.39 ± 1.47 4.73 ± 1.45 <0.01* 4.78 ± 1.46 4.77 ± 1.45 0.33 
ParameterLDL Cholesterol, mg/dLPTriglycerides, mg/dLPHDL Cholesterol, mg/dLP
>150 (n = 119)<150 (n = 589)>250 (n = 53)<250 (n = 651)Low(n = 303)Normal (n = 401)
Age, years 47.71 ± 10.91 52.98 ± 11.59 <0.001* 46.04 ± 10.82 52.59 ± 11.58 <0.01* 51.11 ± 12.08 52.78 ± 11.21 0.05 
Diabetes duration, years 7.66 ± 7.20 9.00 ± 7.60 0.126 5.77 ± 6.38 9.04 ± 7.60 0.01* 7.93 ± 7.09 9.28 ± 7.69 0.18 
BMI, kg/m2 26.42 ± 3.63 26.35 ± 3.84 0.842 25.62 ± 3.77 26.42 ± 3.81 0.15* 26.50 ± 3.72 26.25 ± 3.88 0.22 
Systolic blood pressure, mmHg 130.38 ± 22.30 130.45 ± 17.42 0.973 129.86 ± 21.66 130.48 ± 18.03 0.82 129.18 ± 18.62 131.30 ± 18.03 0.84 
Diastolic blood pressure, mmHg 77.48 ± 9.40 77.60 ± 9.12 0.892 80.43 ± 10.22 77.36 ± 9.04 0.02* 77.47 ± 9.19 77.62 ± 9.14 0.76 
Waist-to-hip ratio 0.98 ± 0.05 0.98 ± 0.11 0.555 0.99 ± 0.05 0.98 ± 0.11 0.26 0.97 ± 0.09 0.97 ± 0.11 0.88 
Hemoglobin, g/dL 13.49 ± 1.63 13.44 ± 1.63 0.731 14.44 ± 1.76 13.37 ± 1.59 <0.01* 13.21 ± 1.78 13.62 ± 1.48 0.005* 
Total leukocyte count, cells/mm3 6,710.00 ± 1,919.53 6,627.69 ± 1,509.83 0.606 7,062.26 ± 1,810.46 6,607.36 ± 1,562.12 0.04* 6,774.25 ± 1,652.47 6,531.27 ± 1,515.21 0.74 
ESR, mm/hour 20.17 ± 19.11 17.02 ± 15.64 0.05 18.98 ± 21.69 17.44 ± 15.83 0.52 19.81 ± 18.29 15.85 ± 14.45 <0.01* 
Cr, mg/dL 1.04 ± 0.69 0.98 ± 0.45 0.255 1.06 ± 0.70 0.99 ± 0.48 0.34 0.99 ± 0.69 0.98 ± 0.27 0.01* 
eGFR, mL/min/1.73 m2 90.87 ± 31.21 91.84 ± 55.15 0.856 100.48 ± 36.90 90.97 ± 52.93 0.20 94.68 ± 60.61 89.23 ± 44.21 0.23 
Urine albumin-to-creatinine ratio, mg/g Cr 60.54 ± 95.29 45.06 ± 75.39 0.052 47.92 ± 68.67 47.68 ± 80.13 0.98 41.04 ± 68.36 52.96 ± 86.54 <0.01* 
TSH, μIU/ml 2.28 ± 1.13 2.15 ± 1.03 0.208 2.19 ± 1.06 2.17 ± 1.04 0.88 2.19 ± 1.04 2.14 ± 1.03 0.98 
AST, IU/L 33.43 ± 48.99 31.84 ± 17.38 0.538 42.38 ± 71.90 31.28 ± 16.87 <0.01* 31.41 ± 18.51 32.57 ± 29.82 0.29 
ALT, IU/L 43.45 ± 49.21 40.35 ± 31.07 0.375 53.30 ± 64.93 39.87 ± 30.94 0.01* 40.09 ± 29.47 41.33 ± 38.34 0.05 
A1C, % 9.13 ± 2.79 8.49 ± 2.27 0.007* 9.34 ± 2.39 8.54 ± 2.37 0.02* 8.59 ± 2.26 8.59 ± 2.46 0.28 
FPG, mg/dL 200.30 ± 88.43 176.38 ± 70.49 0.001* 215.02 ± 87.09 177.61 ± 72.52 < 0.01* 179.94 ± 70.99 180.59 ± 76.79 0.31 
Uric acid, mg/dL 4.83 ± 1.75 4.77 ± 1.40 0.679 5.39 ± 1.47 4.73 ± 1.45 <0.01* 4.78 ± 1.46 4.77 ± 1.45 0.33 

Data are mean ± SD.

*

Statistically significant (P <0.05).

Low HDL is <50 mg/dL in females and <40 mg/dL in males.

Lipid Management for ASCVD Prevention

The statin prescription pattern and achieved level of LDL cholesterol was assessed in patients treated with a statin versus those not taking a statin. Patients already having a label of dyslipidemia were more likely to be on statin therapy than those who were newly diagnosed with dislipidemia (58.2 vs. 16.34%, P <0.05).

Among the 842 patients who were ≥40 years of age (and thus should have been on statin therapy per ADA guidelines), 253 (30.0%) were taking a statin. Of the 129 patients <40 years of age, 17 had a family history of premature ASCVD, 92 had a serum LDL cholesterol level ≥100 mg/dL, 37 had microalbuminuria, and 3 had a low eGFR (<60 mL/min/1.73 m2). Hence, 108 of the 129 patients <40 years age should have been on statin therapy per ADA guidelines (8). Of these 108 patients, 10 (9.25%) were receiving statin therapy. On the whole, of the 950 patients who should have been on statin therapy, only 263 (27.7%) were. Of the 263 patients who were on statin treatment, 112 (42.6%) had an LDL cholesterol ≥100 mg/dL, and 187 (71.1%) had an LDL cholesterol ≥70 mg/dL (Table 4).

TABLE 4

Proportions of Patients in Need of Statin Therapy and Adequacy of Statin-Prescribing Rates

Statin Therapy Status CategoryPatients, %
Patients in need for statin therapy 97.8 
Patients in need of statin therapy who were receiving it 27.7 
Patients <40 years of age in need of statin therapy 83.7 
Patients <40 years in need of statin therapy who were receiving it 9.25 
Total patients receiving adequate lipid-lowering therapy 16.0 
Statin Therapy Status CategoryPatients, %
Patients in need for statin therapy 97.8 
Patients in need of statin therapy who were receiving it 27.7 
Patients <40 years of age in need of statin therapy 83.7 
Patients <40 years in need of statin therapy who were receiving it 9.25 
Total patients receiving adequate lipid-lowering therapy 16.0 

This study was a retrospective evaluation of lipid profile abnormalities and statin prescription rates in South Indian patients with type 2 diabetes. A total of 971 patients with diabetes were included, after excluding those with clinical or subclinical hypothyroidism and other comorbidities or medications likely to affect lipid parameters. The mean age of the population was 53.1 + 11.1 years (range 41–85 years). The mean BMI was 26.8 + 3.9 kg/m2, indicating that the population was overweight but not obese. The population studied had a mean A1C of 8.6 ± 2.3% (Table 2).

Pattern of Dyslipidemia

Conventionally, the most common lipid abnormality in diabetes is thought to be moderate hypertriglyceridemia and low HDL cholesterol (9). In this study, elevated LDL cholesterol was found to be more prevalent than hypertriglyceridemia using cutoffs of LDL ≥150 mg/dL and TG ≥250 mg/dL. High serum LDL cholesterol (≥150 mg/dL) was present in 16.1% of patients.

The ADA’s Standards of Medical Care in Diabetes—2019 (8) identify LDL cholesterol ≥100 mg/dL as a risk factor for ASCVD and <70 mg/dL as the desirable level for individuals with diabetes and established ASCVD or high risk for developing it. Given this recommendation, we assessed the proportion of patients with an LDL cholesterol level ≥70 or ≥100 mg/dL, which were found to be 84.1 and 56.5%, respectively. Only 7.49% of patients had a TG level ≥250 mg/dL, and 29.4% had a TG level ≥150 mg/dL. Low HDL cholesterol per sex-specific cutoff values was observed in 42.8% of patients. The lipid profile pattern observed in this study is similar to those found in studies of lipid control in type 2 diabetes from North Kerala and elsewhere (1014), as shown in Figure 1. The mean values for TG, LDL cholesterol, and HDL cholesterol were comparable to those in the other studies except for those in which glycemic control was poor (11,12).

In this study, higher FPG and A1C values were found to be associated with higher LDL cholesterol and TG levels. These findings are in agreement with other studies that have described the correlation between poor glycemic control and high total cholesterol, TG, and LDL cholesterol levels (15). This observation implies that better glycemic control as evidenced by lower FPG and A1C levels would likely lower LDL cholesterol and TG levels in patients with diabetes; thus, lipid-lowering medications may be deferred until glycemic control is achieved and a real picture of a patient’s lipid pattern emerges.

The post-meal increase in blood glucose (although not based on a standard glucose load in this study) was also associated with higher serum TG levels, indicating that serum TG may be related to day-to-day glycemic excursions in addition to the pervasively high blood glucose levels.

There were no statistically significant associations of higher BMI or waist-to-hip ratio with any of the lipid parameters, although other measures of abdominal adiposity were not studied. The association of elevated ESR with higher LDL and lower HDL cholesterol levels may be an indicator of low-level inflammation contributing to cardiovascular risk (16). Similarly, higher total leukocyte counts were associated with higher TG levels. Higher diastolic blood pressure, AST, and ALT values were found to be associated with higher TG levels, which may suggest a link between insulin resistance and hepatic inflammation.

In this study, the mean age of patients was significantly lower in those with LDL cholesterol ≥150 mg/dL, indicating that young people with diabetes have higher LDL cholesterol levels. The reduction in total cholesterol and LDL cholesterol with age (>65 years) has been described elsewhere (17). This finding could explain why high plasma cholesterol levels are less predictive of heart disease in the elderly than in younger people.

Adequacy of Dyslipidemia Management

Kerala has the highest risk of ASCVD among the Indian states. In a recent study, across India, the mean predicted 10-year risk of a cardiovascular event as calculated with the Framingham risk score varied from 13.2% (95% CI 12.7–13.6%) in Jharkhand to 19.5% (95% CI 19.1–19.9%) in Kerala (1,18). Factors contributing to the high ASCVD risk were higher mean systolic and diastolic blood pressure, BMI, and prevalence of hyperglycemia and smoking (1). In a study from South India, the prevalence of dyslipidemia in people >30 years of age (defined as total cholesterol ≥200 mg/dL, LDL cholesterol ≥130 mg/dL, TG ≥150 mg/dL, and low HDL cholesterol) was very high—74.8% in an urban area and 68% in a rural area studied (2).

The beneficial role of statin therapy in the primary prevention of ASCVD in people with diabetes has been substantiated by multiple well-conducted trials (16,1923). According to the ADA, antihyperlipidemic medications are indicated for all patients with diabetes who are ≥40 years of age and for those <40 years of age who have additional ASCVD risk factors such as a history of ASCVD, a family history of premature ASCVD, LDL cholesterol ≥100 mg/dL, albuminuria, or a low eGFR, and statins are the preferred initial drug class (8). The recommendation of statin therapy in patients who are ≥40 years of age without dyslipidemia or a history of CVD is based on the non–LDL cholesterol targets of statin therapy in diabetes (i.e., high levels of TG, non-HDL cholesterol, and apolipoprotein B, which may contribute to high ASCVD risk [8]).

Of the 950 patients in this study who had a need for statin therapy according to current guidelines, only 27.7% were taking a statin, and of those <40 years of age with a need for statin therapy, only 9.2% were taking one. Other studies in people with diabetes from India and elsewhere have found that statins are under-prescribed (17). In a study from North Carolina, the statin prescription rate in patients with diabetes was 34.7% in people 40–65 years of age and 38.2% in those >65 years of age (5). In the current study, even among those with a statin prescription, only 16% had adequate lipid-lowering therapy.

A cornerstone of diabetes management is the prevention of long-term complications, including ASCVD. The past decade has witnessed the influx of many newer therapies for type 2 diabetes that have been evaluated in cardiovascular outcome trials (24). However, despite the pleotropic effects of such drugs, strong evidence with regard to ASCVD risk reduction, and guidelines advocating early and target-driven prescription of statins, therapeutic inertia continued in the care of people with type 2 diabetes. This phenomenon has been observed in studies throughout the world. One reason for inertia with regard to statins in particular could be a moderately increased risk of incident diabetes with statin use, as reported by several studies (25). However, a meta-analysis has shown that the odds ratio of new-onset diabetes in statin users is only 1.09 and that statin treatment in 255 patients with statins for 4 years would result in only one additional case of diabetes while preventing 5.4 vascular events among those patients (26). Such therapeutic inertia has been described in all stages of treatment intensification from first oral antidiabetic drug to intensification of insulin (27). The current study adds to the available data on therapeutic inertia in diabetes management and reveals an opportunity for further ASCVD risk reduction in the population studied.

One of the limitations of this retrospective study was its reliance on PPG measurements to indicate post-load glycemic excursions rather than a 2-hour plasma glucose measurement during a 75-g oral glucose tolerance test, which might have yielded more accurate data.

In South Indian patients being treated for type 2 diabetes, elevated LDL and low HDL cholesterol are the predominant lipid abnormalities. In this population with high risk of ASCVD, a significant proportion of patients who could benefit from statin therapy were not receiving it. There remains great potential for ASCVD risk reduction in this population, provided this gap in guideline-driven care is acknowledged and rectified.

Acknowledgments

The authors acknowledge the support extended by Remla A, senior scientific officer of the Indian Institute of Diabetes in Trivandrum, in the supervision of biochemical measurements and data management. The authors acknowledge Lekshmi Das, Arya Suresh, Arya Sugesh, and Sudi Sisupalan (research assistants at the Indian Institute of Diabetes and the Department of Endocrinology at Government Medical College in Thiruvananthapuram), T.P. Seena (physiology assistant), and Nandini Prasad, Geena Susan George, and Ajeesh T (senior residents in the Department of Endocrinology at Government Medical College in Thiruvananthapuram) for their roles in patient information retrieval and manuscript preparation.

Funding

This study was funded by the Research Society for the Study of Diabetes in India.

Duality of Interest

No potential conflicts of interest relevant to this article were reported.

Author Contributions

C.J. and A.N. conceived the concept, conducted the study, and contributed to manuscript preparation. P.K.J., R.G., and R.S. reviewed the data and edited the manuscript. S.S. researched the data and wrote the manuscript. R.V.J. contributed to discussion and reviewed the manuscript. D.V.D. contributed to discussion. G.G. and A.G. contributed to data analysis and preparation of the manuscript. A.N. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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