Oxytocin levels are lower in premenopausal women with type 1 diabetes mellitus compared with matched controls

Abstract

Background Oxytocin (OT), a hormone most commonly associated with parturition and lactation, may have additional roles in diabetes complications. We determined OT levels in premenopausal women with type 1 diabetes mellitus (T1DM) compared to nondiabetic controls; and examined associations of OT with health behaviors, clinical factors, biomarkers, kidney function, and bone health. Lower OT was hypothesized for T1DM. Methods Cross-sectional study of premenopausal women with T1DM (n=88) from the Wisconsin Diabetes Registry Study, a population-based cohort of incident T1DM cases, and matched nondiabetic controls (n=74). Results Women with T1DM had lower OT levels than controls adjusting for caffeine and alcohol use (p=0.03). Health behaviors associated with OT differed between women with and without T1DM: OT was negatively associated with hormonal contraceptive use (quantified as lifetime contraceptive estrogen exposure) in women with T1DM (p=0.003) while positively related to hormonal contraceptive use (quantified as never/former/current) in controls (p<0.001). OT had a positive association with adiposity (waist-to-hip ratio and leptin) in women with T1DM and a negative relationship with adiposity (weight gain) in controls. In T1DM only, OT was positively associated with caffeine intake (p=0.01) and negatively associated with alcohol use (p=0.01). OT was not related to glycemic control, kidney function, or bone health in T1DM. Conclusions OT levels are lower in women with T1DM than matched controls. OT also has opposing associations with hormonal contraceptives and adiposity in women with and without T1DM. Research is needed to determine if the altered OT milieu in T1DM is associated with other health outcomes.

Plasma Oxytocin Concentration in Pre- and Postmenopausal Women: Its Relationship with Obesity, Body Composition and Metabolic Variables

“…Similarly, intranasal oxytocin administration to obese and prediabetic patients resulted in a significant decrease of body weight after 4 and 8 weeks of treatment [20]. In line with these evidences, cohort studies investigating oxytocin concentration additionally found an inverse association between oxytocin and obesity, HbA1C levels, insulin resistance as well as T1DM or T2DM, thus emphasizing the potential negative influence of positive energy states on circulating oxytocin [21,22,23]. However, this inference has been recently challenged in a study in premenopausal women with different energy states [24].…”

“…Complimentarily, oxytocin levels have been found decreased in most but not all animal models of obesity and T2DM, including diet-induced-obesity (DIO) and carriers of leptin deficiency [16,36,37]. In cohort studies, oxytocin levels are reportedly similar between genders [22] as well as with regard to decline with age [38], and decrease in obesity and newly diagnosed T2DM [23]. Concordant with evidence that estrogen loss decreases oxytocin levels, our current results show that oxytocin levels are lower in postmenopausal than premenopausal women both in normal-weight and obese conditions, suggesting that an inverse association relates oxytocin to menopause independently of obesity.…”

“…In a search for potential explanatory mechanisms related to our findings, we noted a robust inverse correlation between oxytocin and leptin levels. This relationship is currently argued [10,26,45] and has been shown to be positive in premenopausal women with T1DM [23] and postmenopausal women with osteoporosis [21]. Although leptin and oxytocin act synergistically at the central level to inhibit food intake [19,45], obesity alters this interplay [16,46], and oxytocin administration to obese mice or humans reduces caloric intake devoid of leptin resistance, leading to hypothesize that oxytocin control of body weight could occur independently of leptin-sensitive circuitries [18,47,48].…”

The effects of oxytocin on eating behaviour and metabolism in humans

“…Men and women with type 2 diabetes mellitus 92 and women with type 1 diabetes mellitus 115 have been shown to have lower levels of oxytocin than controls. Furthermore, in those with type 2 diabetes mellitus, low fasting levels of oxytocin were associated with higher levels of glucose and insulin, both after fasting and after an oral glucose tolerance test, as well as higher HOMA-IR results and levels of HbA 1c 92 ; these findings suggest that diabetes mellitus could be a state of oxytocin deficiency.…”

Intranasal oxytocin fails to acutely improve glucose metabolism in obese men

“…In a large sample of men with metabolic syndrome, oxytocin concentrations were elevated compared with healthy controls, whereas the obese subjects of the present experiment displayed lower baseline oxytocin levels than their lean counterparts. Decreased oxytocin concentrations were reported in patients with metabolic syndrome or diabetes mellitus, suggesting a certain degree of oxytocin deficiency in diabetic patients . However, our preliminary finding of a positive relationship between HOMA‐IR and baseline oxytocin concentrations in the obese subjects argues against this assumption.…”