Introduction:
Obesity is associated with type 2 diabetes and coronary artery disease (Riaz et al., 2018). Metformin may have potential for treatment of cardiovascular disease (CVD) but prospective RCTs have been largely neutral on CVD related outcomes (Han et al., 2019). Another meta-analysis showed that metformin could reduce total cholesterol and LDL-c in nondiabetic adults, as well as have a triglyceride-lowering effect in nondiabetic patients with PCOS (Weng et al., 2020). Bariatric surgery reduces all-cause and cardiovascular mortality, as well as reduce CVD in patients with obesity (van Veldhuisen et al., 2022), and also produces improvements in serum lipids (Heffron et al., 2016). We present a patient with obesity and PCOS treated with metformin, and another patient with obesity treated with sleeve gastrectomy, and report changes in various cardiovascular risk biomarkers.
Clinical case:
AH is a 16-year-old female with class 3 obesity (BMI up to 47kg/m2) with prediabetes (hbA1c 6.3%) and whose PCOS was treated with metformin. Her weight stabilised and her insulin sensitivity by HOMA-IR improved, as did uric acid and triglyceride/HDL. sdLDL and total cholesterol/HDL increased slightly (Table 1).
GA is a 36-year-old man with class 3 obesity (BMI up to 70.1kg/m2), who was treated with sleeve gastrectomy. He had significant weight loss with BMI down to 45.7kg/m2 by 8 months post-surgery, with improvements in uric acid, sdLDL, total cholesterol/HDL, triglyceride/HDL, and hbA1c (Table 2).
Table 2. AH’s anthropometry and cardiovascular risk biomarkers.
|
Date |
[Weight (kg), Height (cm)], BMI (kg/m2) |
Waist circ. (cm) |
Uric acid (mmol/L) |
sdLDL (mmol/L) |
[Total chol., HDL], total cho./HDL |
[Trig. (mmol/L), HDL (mmol/L)], trig./HDL |
[Fast. glucose (mmol/L), fast. insulin (mU/L)], HOMA-IR index |
hbA1c (%) |
Management |
|
25/07/20 |
[131.1, 178.8], 41.0 |
|
0.414 |
0.460 |
[2.9, 1.11], 2.61 |
[0.8, 1.11], 0.721 |
[5.1, 47], 10.65 |
|
|
|
16/02/22 |
[151.6, 179.5], 47.0 |
135 |
0.471 |
|
|
|
|
|
Metformin 1000mg daily (early 2022) |
|
08/05/22 |
[148.4, 180.0], 45.9 |
|
|
|
|
|
|
|
|
|
29/12/22 |
|
|
|
|
|
|
[5.7, 43], 10.89 |
6.3 |
Initial review in weight management clinic (Nov 2022) |
|
16/03/23 |
|
|
|
|
|
|
|
|
Commenced dietitian review |
|
25/08/23 |
[150.5, 180.5], 46.2 |
135 |
0.436 |
0.486 |
[3.1, 0.99], 3.13 |
[0.7, 0.99], 0.707 |
[5.1, 20], 4.53 |
6.2 |
Awaiting sleep study (ESS <5 but apnoeic episodes), ongoing psychology review (Head Space) |
(p-values will be added)
Table 1. GA’s anthropometry and cardiovascular risk biomarkers
|
Date |
[Weight (kg), Height (cm)], BMI (kg/m2) |
Waist circ. (cm) |
Uric acid (mmol/L) |
sdLDL (mmol/L) |
[Total chol., HDL], total cho./HDL |
[Trig. (mmol/L), HDL (mmol/L)], trig./HDL |
[Fast. glucose (mmol/L), fast. insulin (mU/L)], HOMA-IR index |
hbA1c (%) |
Management |
|
13/06/18 |
|
|
0.474 |
1.1 |
[5.0, 1.0], 5.0 |
[1.5, 1.0], 1.5 |
[5.4, n/a], n/a |
5.2 |
|
|
14/06/21 |
|
|
0.502 |
|
|
|
[4.7, n/a], n/a |
|
|
|
01/09/22 |
[209.9, 173.0], 70.1 |
|
|
1.2 (non-fasted) |
[5.4, 1.0], 5.4 (non-fasted) |
[1.8, 1.0], 1.8 (non-fasted) |
|
5.4 |
Initial weight management clinic. Referred for private bariatric surgery, dietitian and sleep study (ESS 7/24) à CPAP treatment. |
|
27/10/22 |
[204.8, 173.0], 68.4 |
|
|
|
|
|
|
|
|
|
06/12/22 |
[189.0, 173.0], 63.1 |
|
|
|
|
|
|
|
Gastric sleeve surgery |
|
02/02/23 |
[164.3, 173.0], 54.9 |
146 |
|
(04/02/22) 0.9
|
[3.9, 0.67], 5.8 |
[1.6, 0.67], 2.4 |
[4.8, n/a], n/a |
5.3 |
|
|
10/08/23 |
[136.8, 173.0], 45.7 |
146 |
(16/06/23) 0.471 |
0.8
|
[4.6, 0.97], 4.7 |
[0.9, 0.97], 0.9 |
[4.2, 7], 1.31 |
5.1 |
Discharged from weight management clinic |
(p-values will be added)
Conclusion:
Treatment with metformin in patient AH showed improvement in insulin sensitivity by HOMA-IR but no uniform improvements in lipid biomarkers. Sleeve gastrectomy in patient GA resulted in significant weight loss, and improvement in uric acid and lipid biomarkers.
Further studies are needed to better understand the influence of metformin and other modalities of weight loss on alternate CV biomarkers (Thupakula et al., 2022). Such a study is currently in early progress at Townsville University Hospital.