Insulin resistance before diabetes onset may increase risk of albuminuria after diabetes onset: Study

The findings, published in Diabetes, Obesity and Metabolism on February 28, 2024, highlight the potential of improving insulin signaling as a therapeutic strategy.

The study implies that maintaining good insulin action is important for preventing albuminuria onset and reducing the risk of kidney and cardiovascular diseases, particularly in nondiabetic individuals.

Albuminuria is a risk factor for cardiovascular (CV) events and mortality in the general population and among patients with diabetes mellitus. Understanding the pathophysiology of albuminuria is critical for targeting interventions to reduce albuminuria and accompanying outcomes. Reduced renal insulin signaling is implicated in the albuminuria pathogenesis.

Longitudinal studies linking insulin action and subsequent albuminuria risk are limited. Therefore, Douglas C. Chang, National Institutes of Health, Phoenix, Arizona, USA, and colleagues aimed to investigate whether insulin secretion and action, measured before diabetes onset, are associated with albuminuria development after diabetes onset.

For this purpose, the researchers measured Baseline body composition, insulin sensitivity by a hyperinsulinaemic-euglycaemic clamp at submaximal and maximal insulin stimulation (240 and 2400 pmol/m2/min; M-low and M-high), and insulin secretion by intravenous glucose tolerance test [acute insulin response (AIR)] in 170 Southwestern Indigenous American adults who subsequently developed diabetes.

After diabetes onset and during the median follow-up of 13.6 years, 81 participants developed albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g). Separate associations of M-low, M-high, and AIR (per 1-SD change) with albuminuria risk were assessed by Cox regression models adjusted for sex, age, and body fat (%).

The researchers reported the following findings:

• Participants who developed albuminuria were of similar age (26.4 ± 5.4 vs. 27.5 ± 6.1 years), sex (46% vs. 48% male), body fat (36.4 ± 7.5 vs. 35.7 ± 7.9%) and AIR [2.3 ± 0.3 vs. 2.3 ± 0.3, pmol/L (log)] as those who did not develop albuminuria but had lower insulin sensitivity [M-low: 0.33 ± 0.08 vs. 0.36 ± 0.12; M-high: 0.87 ± 0.11 vs. 0.91 ± 0.12, p = .02; mg/kg-metabolic body size/min (log)].
• In separate adjusted models, lower M-low and M-high were both associated with an increased risk for albuminuria [hazard ratio (HR) 1.51, HR 1.31), whereas AIR was not (HR 1.15).

In conclusion, lower insulin action in Indigenous Americans without diabetes is a risk factor in albuminuria development after diabetes onset.

"These findings indicate insulin signaling as a possible therapeutic target for preventing cardiovascular and kidney disease," the researchers wrote.

Reference:

Willig MR, Stinson EJ, Looker HC, et al. Insulin resistance before type 2 diabetes onset is associated with increased risk of albuminuria after diabetes onset: A prospective cohort study. Diabetes Obes Metab. 2024;1‐9. doi:10.1111/dom.15505