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

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