Sex differences in intraorgan fat levels and hepatic lipid metabolism: implications for cardiovascular health and remission of type 2 diabetes after dietary weight loss

Aims/hypothesis Type 2 diabetes confers a greater relative increase in CVD risk in women compared with men. We examined sex differences in intraorgan fat and hepatic VLDL1-triacylglycerol (VLDL1-TG) export before and after major dietary weight loss. Methods A group with type 2 diabetes (n = 64, 30 male/34 female) and a group of healthy individuals (n = 25, 13 male/12 female) were studied. Intraorgan and visceral fat were quantified by magnetic resonance and VLDL1-TG export by intralipid infusion techniques. Results Triacylglycerol content of the liver and pancreas was elevated in people with diabetes with no sex differences (liver 16.4% [9.3–25.0%] in women vs 11.9% [7.0–23.1%] in men, p = 0.57, and pancreas 8.3 ± 0.5% vs 8.5 ± 0.4%, p = 0.83, respectively). In the absence of diabetes, fat levels in both organs were lower in women than men (1.0% [0.9–1.7%] vs 4.5% [1.9–8.0%], p = 0.005, and 4.7 ± 0.4% vs 7.6 ± 0.5%, p< 0.0001, respectively). Women with diabetes had higher hepatic VLDL1-TG production rate and plasma VLDL1-TG than healthy women (559.3 ± 32.9 vs 403.2 ± 45.7 mg kg−1 day−1, p = 0.01, and 0.45 [0.26–0.77] vs 0.25 [0.13–0.33] mmol/l, p = 0.02), whereas there were no differences in men (548.8 ± 39.8 vs 506.7 ± 29.2 mg kg−1 day−1, p = 0.34, and 0.72 [0.53–1.15] vs 0.50 [0.32–0.68] mmol/l, p = 0.26). Weight loss decreased intraorgan fat and VLDL1-TG production rates regardless of sex, and these changes were accompanied by similar rates of diabetes remission (65.4% vs 71.0%) and CVD risk reduction (59.8% vs 41.5%) in women and men, respectively. Conclusions/interpretation In type 2 diabetes, women have liver and pancreas fat levels as high as those of men, associated with raised hepatic VLDL1-TG production rates. Dynamics of triacylglycerol turnover differ between sexes in type 2 diabetes and following weight loss. These changes may contribute to the disproportionately raised cardiovascular risk of women with diabetes. Graphical abstract

Fetuin-B, a potential link of liver-adipose tissue cross talk during diet-induced weight loss–weight maintenance

Background/objectives Numerous hepatokines are involved in inter-organ cross talk regulating tissue-specific insulin sensitivity. Adipose tissue lipolysis represents a crucial element of adipose insulin sensitivity and is substantially involved in long-term body weight regulation after dietary weight loss. Thus, we aimed to analyze the impact of the hepatokine Fetuin-B in the context of weight loss induced short- and long-term modulation of adipose insulin sensitivity. Subjects/methods 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before (T-3) and after (T0) a standardized 12-week dietary weight reduction program. Afterward, subjects were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until 6 months later (T18) (Maintain-Adults trial). Tissue-specific insulin sensitivity was estimated by HOMA-IR (predominantly liver), ISIClamp (predominantly skeletal muscle), and free fatty acid suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). Fetuin-B was measured at all concomitant time points. Results Circulating Fetuin-B levels correlated significantly with estimates of obesity, hepatic steatosis as well as HOMA-IR, ISIClamp, FFASupp at baseline. Fetuin-B decreased during dietary weight loss (4.2 (3.5–4.9) vs. 3.8 (3.2–4.6) µg/ml; p = 2.1 × 10−5). This change was associated with concomitant improvement of HOMA-IR (r = 0.222; p = 0.008) and FFASupp (r = −0.210; p = 0.013), suggesting a particular relationship to hepatic and adipose tissue insulin sensitivity. Weight loss induced improvements of insulin resistance were almost completely preserved until months 12 and 18 and most interestingly, the short and long-term improvement of FFASupp was partially predicted by baseline level of Fetuin-B. Conclusions Our data suggest that Fetuin-B might be a potential mediator of liver-adipose cross talk involved in short- and long-term regulation of adipose insulin sensitivity, especially in the context of diet-induced weight changes. Trial registration ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.

A feasibility study to test a novel approach to dietary weight loss with a focus on assisting informed decision making in food selection

Obesity is a significant contributor to the development of chronic diseases, some of which can be prevented or reversed by weight loss. However, dietary weight loss programs have shortcomings in success rate and magnitude or sustainability of weight loss. The objective of the Individualized Diet Improvement Program (iDip) was to test the feasibility of a novel approach that helps individuals self-select a sustainable diet for weight loss and maintenance instead of providing weight loss products or rigid diet instructions to follow. The iDip study consisted of 22 dietary improvement sessions over 12 months with six months of follow-up. Daily weights were collected, and a chart summarizing progress was provided weekly. Six 24-hour dietary records were collected, and dietary feedback was provided in the form of a protein-fiber plot, in which protein/energy and fiber/energy of foods were plotted two-dimensionally together with a target box specific to weight loss or maintenance. An exit survey was conducted at 12 months. Twelve (nine female, 46.3±3.1 years (mean±SE)) of the initial 14 participants (BMI>28 kg/m2) completed all sessions. Mean percent weight loss (n=12) at six and 12 months was -4.9%±1.1 (p=0.001) and -5.4%±1.7 (p=0.007), respectively. Weight loss varied among individuals at 12 months; top and bottom halves (n=6 each) achieved -9.7%±1.7 (p=0.0008) and -1.0%±1.4 weight loss, respectively. The 24-hour records showed a significant increase in protein density from baseline to final (4.1g/100kcal±0.3 vs. 5.7g/100kcal±0.5 (p=0.008)). Although mean fiber density showed no significant change from the first month (1.3g/100kcal±0.1), the top half had significantly higher fiber/energy intake than the bottom half group. The survey suggested that all participants valued the program and its individualized approach. In conclusion, half of the participants successfully lost >5% and maintained the lost weight for 12 months without strict diet instructions, showing the feasibility of the informed decision-making approach.

Effect of Weight Loss by Low-Calorie Diet on Cardiovascular Health in Type 2 Diabetes: An Interventional Cohort Study

Cardiovascular disease (CVD) remains a major problem for people with type 2 diabetes (T2DM), and the leading cause of death worldwide. We aimed to determine cardiovascular benefits of weight loss with or without remission of diabetes, and to assess utility of plasma biomarkers. 29 people with T2DM were studied at baseline and after dietary weight loss. Change in plasma adipokines and lipid related markers was examined in relation to weight loss, diabetes remission, 10-year cardiovascular risk (QRISK), and duration of diabetes. QRISK decreased markedly after weight loss (18.9 ± 2.2 to 11.2 ± 1.6%, p < 0.0001) in both responders and non-responders, but non-responders remained at higher risk (15.0 ± 2.0 vs. 5.8 ± 1.6%, p < 0.0001). At baseline, plasma GDF-15 was higher in longer diabetes duration (1.19 ± 0.14 vs. 0.82 ± 0.09 ng/mL, p = 0.034), as was the QRISK (22.8 ± 2.6 vs. 15.3 ± 3.4%, p = 0.031). Leptin, GDF-15 and FGF-21 decreased whereases adiponectin increased after weight loss in responders and non-responders. However, the level of FGF-21 remained higher in non-responders (0.58 [0.28–0.71] vs. 0.25 [0.15–0.42] ng/mL, p = 0.007). QRISK change correlated with change in plasma VLDL1-TG (r = 0.489, p = 0.007). There was a positive correlation between rise in HDL cholesterol and the decrease in leptin (r = 0.57, p = 0.001), or rise in adiponectin (r = 0.58, p = 0.001) levels. In conclusion, weight loss markedly decreases cardiometabolic risk particularly when remission of diabetes is achieved. Leptin, adiponectin, GDF-15 and FGF-21 changes were related to weight loss not remission of diabetes. Normalization of 10-year cardiovascular risk and heart age is possible after substantial dietary weight loss and remission of T2DM.

Abdominoplasty in the Massive Weight Loss Patient: Are Aesthetic Goals and Safety Mutually Exclusive?

Background The goals of abdominoplasty in massive weight loss (MWL) patients are often functional, with a greater emphasis on safety than on aesthetic rejuvenation. As important as functional improvements and safety are, however, there may be room for increasing the aesthetic potential of abdominoplasties in these patients. Objectives To determine the safety of the pursuit of aesthetic goals for abdominoplasty in MWL patients. Methods This is a retrospective study examining 910 consecutive female patients consisting of three groups: postpartum (n=718), dietary MWL (n=65) and bariatric MWL (n=127). All patients were approached with a well-defined set of aesthetic goals which were pursued as needed and as feasible. Results The utilization of aesthetic abdominoplasty components was similar all groups, supporting the assertion that the groups were subjected to a similar aesthetic emphasis. Logistic regression showed that a history of bariatric MWL was an independent risk factor for multiple complications (OR 2.738, p=0.014), and that elevated BMI, smoking, diabetes and age were likewise independent risk factors for complications. Propensity score matched case-control pairs showed that bariatric MWL patients were more likely than dietary MWL patients to experience multiple complications (9.52% vs 0 percent, p=0.031). Conclusions Bariatric MWL patients but not dietary weight loss patients seem to have higher risk than postpartum patients. Other comorbidities (elevated BMI, smoking, diabetes, age) seem to be more important predictors of complications than MWL status. Select MWL patients can likely be approached with an emphasis on aesthetic goals, without increasing risks as compared to the postpartum population.

Feasibility of a Culturally Adapted Dietary Weight-Loss Intervention among Ghanaian Migrants in Berlin, Germany: The ADAPT Study

Background: Dietary weight-loss interventions often fail among migrant populations. We investigated the practicability and acceptability of a culturally adapted dietary weight-loss intervention among Ghanaian migrants in Berlin. Methods: The national guidelines for the treatment of adiposity were adapted to the cultural characteristics of the target population, aiming at weight-loss of ≥2.5 kg in 3 months using food-based dietary recommendations. We invited 93 individuals of Ghanaian descent with overweight or obesity to participate in a 12-weeks intervention. The culturally adapted intervention included a Ghanaian dietician and research team, one session of dietary counselling, three home-based cooking sessions with focus on traditional Ghanaian foods, weekly smart-phone reminders, and monthly monitoring of diet and physical activity. We applied a 7-domains acceptability questionnaire and determined changes in anthropometric measures during clinic-based examinations at baseline and after the intervention. Results: Of the 93 invitees, five participants and four family volunteers completed the study. Reasons for non-participation were changed residence (13%), lack of time to attend examinations (10%), and no interest (9%); 64% did not want to give any reason. The intervention was highly accepted among the participants (mean range: 5.3–6.0 of a 6-points Likert scale). Over the 12 weeks, median weight-loss reached −0.6 kg (range: +0.5, −3.6 kg); the diet was rich in meats but low in convenience foods. The median contribution of fat to daily energy intake was 24% (range: 16–40%). Conclusions: Acceptance of our invitation to the intervention was poor but, once initiated, compliance was good. Assessment centers in the participants’ vicinity and early stakeholder involvement might facilitate improved acceptance of the invitation. A randomized controlled trial is required to determine the actual effects of the intervention.