Abstract
PurposeSweetened beverage consumption is associated with type 2 diabetes (T2D) and LADA. We investigated to what extent this association is mediated by BMI and whether it is modified by genotypes of HLA, TCF7L2 rs7903146, or FTO rs9939609.MethodsSwedish case–control data including incident cases of LADA (n = 386) and T2D (n = 1253) with matched population-based controls (n = 1545) was used. We estimated adjusted ORs of diabetes (95% CI) in relation to sweetened beverage intake (per daily 200 mL serving) and genotypes. The impact of BMI was estimated using causal mediation methodology. Associations with HOMA-IR and HOMA-B were explored through linear regression.ResultsSweetened beverage intake was associated with increased risk of LADA (OR 1.15, 95% CI 1.03–1.29) and T2D (OR 1.21, 1.11–1.32). BMI was estimated to mediate 17% (LADA) and 56% (T2D) of the total risk. LADA was associated with risk variants of HLA (3.44, 2.63–4.50) and TCF7L2 (1.27, 1.00–1.61) but not FTO. Only among non-carriers of high-risk HLA genotypes was sweetened beverage intake associated with risk of LADA (OR 1.32, 1.06–1.56) and HOMA-IR (beta = 0.162, p = 0.0047). T2D was associated with TCF7L2 and FTO but not HLA, and the risk conferred by sweetened beverages appeared modified by FTO (OR 1.45, 95% CI 1.21–1.73 in non-carriers).ConclusionsOur findings suggest that sweetened beverages are associated with LADA and T2D partly through mediation by excess weight, but possibly also through other mechanisms including adverse effects on insulin sensitivity. These effects seem more pronounced in individuals without genetic susceptibility.
Highlights
Sweetened beverage consumption has been associated with increased risk of type 2 diabetes (T2D) [1] and childhood type 1 diabetes (T1D) [2]
Sweetened beverage intake did not differ between latent autoimmune diabetes in adults (LADA) and T2D patients (p = 0.9666), but was higher among cases compared to controls (0.59 vs. 0.28 servings/day, p < 0.0001)
Our findings indicate that sweetened beverage intake, in addition to its effect on overweight, may have a direct effect on the risk of both T2D and LADA and that this effect may be exerted through insulin resistance
Summary
Sweetened beverage consumption has been associated with increased risk of type 2 diabetes (T2D) [1] and childhood type 1 diabetes (T1D) [2]. One proposed mechanism for its association with diabetes is that high consumption of sweetened beverages may lead to excess energy intake resulting in increased BMI [4], which in turn is a strong risk factor for T2D [5], and for autoimmune diabetes [6, 7]. A recent meta-analysis found sweetened beverage intake to be associated with increases in fasting glucose and insulin [15]. Another gene of potential interest is the fat mass and obesity-associated (FTO) gene, which has been associated with overweight [16], possibly through alterations in satiety perception, energy intake [17], and nutrient preferences [18], and associates with risk of T2D [19]. Whether the association between sweetened beverages and autoimmune diabetes in adults is modified by genetic susceptibility has not been investigated previously
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