Association Between Obesity and Microvascular Diseases in Patients With Type 2 Diabetes Mellitus

Abstract

This study aimed to evaluate the association between obesity, evaluated by fat mass index (FMI) with the risk of microvascular diseases in patients with type 2 diabetes mellitus (T2DM) and compare the magnitude of associations of FMI, body mass index (BMI), and waist circumference (WC) with the risk of microvascular diseases. We performed a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes study. The primary microvascular outcomes of the present study included chronic kidney disease (CKD) progression, retinopathy, and neuropathy. Cox proportional-hazards models were performed to evaluate the association of FMI with microvascular diseases. A discordant analysis was performed to compare the magnitude of associations of FMI, BMI, and WC with the risk of microvascular diseases. Our study included 10,251 T2DM participants with a median of 5 years (interquartile range, 4.2–5.7) of follow-up. A total of 6,184 participants developed CKD progression, 896 participants had retinopathy, and 3,213 participants developed neuropathy (Michigan Neuropathy Screening Instrument, >2.0). After the confounding factors were adjusted for, patients in the highest FMI quartile had a higher risk of CKD progression (HR: 1.26, 95%CI: 1.16–1.36) and neuropathy (HR: 1.93, 95% CI: 1.74–2.15), except for retinopathy (HR: 1.17, 95% CI: 0.96–1.43), than those in the lowest quartile. Discordant analyses found that FMI and WC are better in identifying individuals with obesity-related risk of neuropathy, compared with BMI; neither is better in identifying individuals with obesity-related risk of CKD progression and retinopathy. Obesity is associated with CKD progression and neuropathy in T2DM participants. Further randomized trials are needed to test whether obesity control can improve the outcomes of T2DM participants with CKD or neuropathy. FMI and WC are more useful in identifying obesity-related risk of neuropathy compared with BMI in T2DM patients.Clinical Trial Registrationhttp://www.clinicaltrials.gov, NCT00000620.

Waist Circumference and Body Mass Index Variability and Incident Diabetic Microvascular Complications: A Post Hoc Analysis of ACCORD Trial (Diabetes Metab J 2022;46:767-80)

“…Hence, patients with T2DM could decrease their risk of developing microvascular complications by maintaining optimal body weight. Surprisingly though, while this observation was true for neuropathy and nephropathy risk, no significant relationship was observed between high weight variability and retinopathy risk, suggesting that weight variability may exhibit a different relationship with microvascular complication risk, as also shown by Gao et al [ 2 ].…”

Lower Visceral Fat Area in Patients with Type 2 Diabetic Peripheral Neuropathy

“…Obesity, especially abdominal obesity, has been proven to be a potential risk factor for the development of diabetic macro-and microvascular complications, including DPN, [2][3][4][5][6][7] but the mechanisms underlying the associations are multifactorial and still unclear. It has been well established that visceral adipose tissue (VAT) can overproduce several bioactive pro-inflammatory cytokines and adipocytokines that lead to IR, metabolic disorders, chronic inflammation, oxidative stress, endothelial dysfunction, and atherosclerotic vascular damage, subsequently resulting in nerve ischemia and direct axonal injury.…”

“…Numerous studies have demonstrated that obesity, especially visceral adiposity, plays an important role in the onset and development of DPN. 6,42 Visceral adiposity, commonly assessed by WC, could contribute to IR, hyperglycaemia, dyslipidemia, hypertension, chronic inflammation and oxidative stress, 43,44 and has been reported to be associated with damaged nerve conduction velocity and higher DPN risk. 45 VFA, which can provide relatively accurate estimates of VAT, might also be correlated with DPN.…”

Waist Circumference and Body Mass Index Variability and Incident Diabetic Microvascular Complications: A Post Hoc Analysis of ACCORD Trial (Diabetes Metab J 2022;46:767-80)

“…However, the association between obesity and microvascular complications in patients with type 2 diabetes mellitus (T2DM) remains controversial. Prior experimental studies suggest that obesity may result in endothelial dysfunction; however, limited epidemiological studies have examined the association between obesity and microvascular diseases, such as retinopathy, nephropathy, and neuropathy, in patients with T2DM [ 1 ]. Several post-hoc analyses of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study data have explored the role of obesity in microvascular complications in patients with T2DM.…”

“…Several post-hoc analyses of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study data have explored the role of obesity in microvascular complications in patients with T2DM. In 2021, Gao et al [ 1 ] investigated the associations between obesity measured using body mass index (BMI), waist circumference (WC), and fat mass index (FMI) and risk of microvascular complications in individuals with T2DM who participated in the ACCORD study. Patients in the highest FMI quartile had a greater risk of nephropathy and neuropathy but not retinopathy compared to those in the lowest quartile [ 1 ].…”