Alterations in glucose and insulin resistance following stress and alcohol cues predict alcohol craving in those with <scp>AUD</scp> and obesity: A preliminary study

BACKGROUND: Alcohol use disorders (AUD) and obesity (OB) are highly prevalent and often comorbid. Recent evidence suggests potential mechanistic overlap that may impact treatments such as Glucagon-like Peptide 1 receptor agonists (GLP1-RAs) for AUD. While alcohol intake can affect blood glucose control, and chronic alcohol use increases diabetes risk, the interplay between obesity, metabolic function, and provoked alcohol craving in AUD has not been previously assessed. Thus, we asked whether AUD and AUD + OB showed distinct patterns of fasting glucose, insulin, and insulin resistance (HOMA) relative to healthy controls and whether these patterns affect provoked alcohol cravings. METHODS: We performed a secondary data analysis of a prior trial of thirty-one 1-month abstinent, inpatient treatment-engaged individuals with AUD (AUD + OB = 7/31) and 41 nonpsychiatric healthy controls (HC + OB = 8/41) who completed 3-day inpatient fasting morning laboratory sessions where they were exposed to stress, alcohol, or neutral-relaxing cues. Repeated assessments of alcohol craving and blood samples to assess insulin and glucose were collected at each laboratory session. Linear mixed models (LMEs) tested interactions between group (AUD vs. HC), lab condition, time points and obesity. RESULTS: The AUD group showed higher glucose levels relative to HC (p = 0.0054). Across laboratory sessions, there were Group (AUD/HC) by Obesity (OB vs. non-OB) interactions for insulin (p = 0.0013) and HOMA (p = 0.0052), where AUD + OB had lower HOMA and insulin levels than HC + OB, but no differences in AUD versus HC groups without obesity were observed. Finally, we found that glucose and HOMA were associated with provoked stress- and alcohol cue-related craving only in the AUD + OB group (all ps < 0.004), with greater glucose and HOMA associated with higher provoked cravings. CONCLUSIONS: These preliminary, hypothesis-generating results suggest that individuals with AUD and obesity may have metabolic alterations that contribute to greater alcohol craving and risk of relapse, and support further testing of GLP-1 agonists for AUD in those with AUD and obesity.