Factors associated with body weight gain and insulin-resistance: a longitudinal study

• Published in: Nutrition & diabetes Vol. 14; no. 1; pp. 21 - 7
• Main Authors: Buscemi, Carola, Randazzo, Cristiana, Barile, Anna Maria, Bo, Simona, Ponzo, Valentina, Caldarella, Rosalia, Malavazos, Alexis Elias, Caruso, Roberta, Colombrita, Piero, Lombardo, Martina, Buscemi, Silvio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-04-2024; Nature Publishing Group
• Subjects: 692/163/2743/393; 692/308/174; Acyltransferases; Adult; Body Mass Index; Clinical Nutrition; Diabetes; Diet; Energy Intake; Epidemiology; Female; Genotype; Humans; Insulin - blood; Insulin resistance; Insulin Resistance - physiology; Internal Medicine; Lipase - genetics; Longitudinal Studies; Male; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Metabolic Diseases; Middle Aged; Obesity - genetics; Phospholipases A2, Calcium-Independent; Weight Gain - physiology
• ISSN: 2044-4052; 2044-4052
• DOI: 10.1038/s41387-024-00283-5

Background
Obesity is the result of energy intake (EI) chronically exceeding energy expenditure. However, the potential metabolic factors, including insulin resistance, remain unclear. This study longitudinally investigated factors associated with changes in body weight.
Subjects
A cohort of 707 adults without diabetes were investigated at the 4-year follow-up visit. The habitual intake of energy and macronutrients during the past 12 months was assessed using a validated Food Frequency Questionnaire for the local population. Homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR) was used as a surrogate measure of insulin resistance. Additionally,
PNPLA3
was genotyped.
Results
Eighty-seven participants were weight gainers (G; cutoff value = 5 kg), and 620 were non-gainers (NG). Initial anthropometric (G vs. NG: age, 44 ± 13 vs 51 ± 13 years,
P
 < 0.001; body mass index, 27.8 ± 6.5 vs 28.1 ± 5.1 kg/m
2
,
P
 = ns; body weight, 76.7 ± 22.1 vs 74.2 ± 14.7 kg,
P
 = ns; final body weight, 86.3 ± 23.7 vs 72.9 ± 14.2 kg,
P
 < 0.001) and diet characteristics, as well as insulin concentrations and HOMA-IR values, were similar in both groups. Four years later, G showed significantly increased EI, insulin concentrations, and HOMA-IR values. G had a higher prevalence of the PNPLA3 CG and GG alleles than NG (
P
 < 0.05). The presence of G was independently associated with age (OR = 1.031), EI change (OR = 2.257), and unfavorable alleles of PNPLA3 gene (OR = 1.700). Final body mass index, waist circumference, and EI were independently associated with final HOMA-IR (
P
 < 0.001).
Conclusions
EI is associated with body weight gain, and genetic factors may influence the energy balance. Insulin resistance is a consequence of weight gain, suggesting a possible intracellular protective mechanism against substrate overflow.
Clinical trial registration
ISRCTN15840340.