Two Patterns of Adipokine and Other Biomarker Dynamics in a Long-Term Weight Loss Intervention

Objective: Long-term dietary intervention frequently induces a rapid weight decline followed by weight stabilization/regain. Here, we sought to identify adipokine biomarkers that may reflect continued beneficial effects of dieting despite partial weight regain. Research design and methods: We analyzed the dynamics of fasting serum levels of 12 traditional metabolic biomarkers and novel adipokines among 322 participants in the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT) of low-fat, Mediterranean, or low-carbohydrate diets for weight loss. Results: We identified two distinct patterns: Pattern A includes biomarkers (insulin, triglycerides, leptin, chemerin, monocyte chemoattractant protein 1, and retinol-binding protein 4) whose dynamics tightly correspond to changes in body weight, with the trend during the weight loss phase (months 0–6) going in the opposite direction to that in the weight maintenance/regain phase (months 7–24) (P < 0.05 between phases, all biomarkers). Pattern B includes biomarkers (high molecular weight adiponectin, HDL cholesterol [HDL-C], high-sensitivity C-reactive protein [hsCRP], fetuin-A, progranulin, and vaspin) that displayed a continued, cumulative improvement (P < 0.05 compared with baseline, all biomarkers) throughout the intervention. These patterns were consistent across sex, diabetic groups, and diet groups, although the magnitude of change varied. Hierarchical analysis suggested similar clusters, revealing that the dynamic of leptin (pattern A) was most closely linked to weight change and that the dynamic of hsCRP best typified pattern B. Conclusions: hsCRP, HDL-C, adiponectin, fetuin-A, progranulin, and vaspin levels display a continued long-term improvement despite partial weight regain. This may likely reflect either a delayed effect of the initial weight loss or a continuous beneficial response to switching to healthier dietary patterns

Renal Function Following Three Distinct Weight Loss Dietary Strategies During 2 Years of a Randomized Controlled Trial

OBJECTIVE This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes. RESEARCH DESIGN AND METHODS In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m2; mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m2; mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR <60 mL/min/1.73 m2 (+7.1%) versus eGFR ≥60 mL/min/1.73 m2 (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = −0.211; P = 0.004) and systolic blood pressure (β = −0.25; P < 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of −24.8 (P < 0.05). CONCLUSIONS A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine <176 μmol/L. Potential improvement is likely to be mediated by weight loss–induced improvements in insulin sensitivity and blood pressure

The Effect of Weight-Loss Interventions on Cervical and Chin Subcutaneous Fat Depots; the CENTRAL Randomized Controlled Trial

Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/− physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m2) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (−13.1% and −5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (−5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10; p = 0.05), HbA1c (β = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16; p = 0.02) and leptin (β = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724

Abdominal Superficial Subcutaneous Fat

OBJECTIVE: Unlike visceral adipose tissue (VAT), the association between subcutaneous adipose tissue (SAT) and obesity-related morbidity is controversial. In patients with type 2 diabetes, we assessed whether this variability can be explained by a putative favorable, distinct association between abdominal superficial SAT (SSAT) (absolute amount or its proportion) and cardiometabolic parameters. RESEARCH DESIGN AND METHODS: We performed abdominal magnetic resonance imaging (MRI) in 73 patients with diabetes (mean age 58 years, 83% were men) and cross-sectionally analyzed fat distribution at S1-L5, L5-L4, and L3-L2 levels. Patients completed food frequency questionnaires, and subgroups had 24-h ambulatory blood pressure monitoring and 24-h ambulatory electrocardiography. RESULTS: Women had higher %SSAT (37 vs. 23% in men; P < 0.001) despite a similar mean waist circumference. Fasting plasma glucose (P = 0.046) and HbA1c (P = 0.006) were both lower with increased tertile of absolute SSAT. In regression models adjusted for age, waist circumference, and classes of medical treatments used in this patient population, increased %SSAT was significantly associated with decreased HbA1c (β = −0.317; P = 0.013), decreased daytime ambulatory blood pressure (β = −0.426; P = 0.008), and increased HDL cholesterol (β = 0.257; P = 0.042). In contrast, increased percent of deep SAT (DSAT) was associated with increased HbA1c (β = 0.266; P = 0.040) and poorer heart rate variability parameters (P = 0.030). Although total fat and energy intake were not correlated with fat tissue distribution, increased intake of trans fat tended to be associated with total SAT (r = 0.228; P = 0.05) and DSAT (r = 0.20; P = 0.093), but not with SSAT. CONCLUSIONS: Abdominal SAT is composed of two subdepots that associate differently with cardiometabolic parameters. Higher absolute and relative distribution of fat in abdominal SSAT may signify beneficial cardiometabolic effects in patients with type 2 diabetes

Acute Myocardial Infarction with Simultaneous Gastric Perforation

Acute myocardial infarction and perforated peptic ulcer disease with associated peritonitis are bothmedical emergencies requiring urgent intervention. This patient presented with both emergenciessimultaneously. Current literature is devoid of guidance as to which should be addressed initially. Amultidisciplinary discussion was conducted leading to a unanimous decision for initiating percutaneouscoronary intervention (PCI). After successful PCI, the patient was immediately taken to the operatingroom for laparoscopic repair of the perforated viscous. Subsequent to the operative repair, the patientbecame hemodynamically unstable and a repeat electrocardiogram demonstrated complete rightcoronary occlusion. Shock ensued and the patient died in the intensive care unit despite this plan ofcare. It is our opinion that this case reveals the need for expert panels to devise decision algorithms forconcomitant presentations of life-threatening diseases

Acute Myocardial Infarction with Simultaneous Gastric Perforation

Acute myocardial infarction and perforated peptic ulcer disease with associated peritonitis are bothmedical emergencies requiring urgent intervention. This patient presented with both emergenciessimultaneously. Current literature is devoid of guidance as to which should be addressed initially. Amultidisciplinary discussion was conducted leading to a unanimous decision for initiating percutaneouscoronary intervention (PCI). After successful PCI, the patient was immediately taken to the operatingroom for laparoscopic repair of the perforated viscous. Subsequent to the operative repair, the patientbecame hemodynamically unstable and a repeat electrocardiogram demonstrated complete rightcoronary occlusion. Shock ensued and the patient died in the intensive care unit despite this plan ofcare. It is our opinion that this case reveals the need for expert panels to devise decision algorithms forconcomitant presentations of life-threatening diseases

Intramyocellular Triacylglycerol Accumulation Across Weight Loss Strategies; Sub-Study Of The Central Trial

Background: Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among participants with abdominal fat, remain unclear. Methods: In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28gday-1 of walnuts). After 6-months, the participants were re-randomized to moderate intense physical activity (PA+) or non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats. Results: Across the 277 participants [86% men, age = 48 years, body-mass-index (BMI) = 31kg/m2, visceral fat = 33%] 86% completed the 18-m trial. At baseline, women had higher IMTG than men (3.4% vs. 2.3%, p\u3c0.001) and increased IMTG was associated with aging and higher BMI, visceral and intermuscular fats, HbA1c%, HDL-c and leptin(p\u3c0.05), but not with intra-hepatic fat. After 18 month of intervention and a -3 kg mean weight loss, participants significantly increased IMTG by 25%, with a distinct effect in the MED/LCPA+ group as compared to the other intervention groups (57% vs. 9.5–18.5%, p\u3c0.05). Changes in IMTG were associated with visceral and intermuscular fat, metabolic syndrome, insulin and leptin (p\u3c0.05 for all), however, these associations did not remain after adjustment for visceral fat changes. Conclusions: Lifestyle strategies differentially affect IMTG accumulation; combination of exercise with decreased carbohydrate/increased unsaturated fat proportion intake greatly increase IMTG. Our findings suggest that increased IMTG during diet-induced moderate weight loss may not be directly related to cardiometabolic risk. Trial registration: ClinicalTrials.gov NCT0153072