Impact of interventions for obesity on insulin sensitivity using the leptin to adiponectin ratio
Rafey, Mohammed Faraz
Rafey, Mohammed Faraz
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Publication Date
2021-11-13
Keywords
BMI, Leptin, Adiponectin, Milk Diet programme, Sleeve Gastrectomy, Insulin sensitivity, Insulin resistance, Leptin to Adiponectin ratio, LAR, Type 2 Diabetes Mellitus, T2DM, Meal replacement programme, hypocaloric diet, Severe obesity, lifestyle modification, Bariatric, Milk, Obesity, Obesity treatment, Medicine, Nursing and Health Sciences, Medicine
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Thesis
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Abstract
Introduction: Low energy meal replacement regimens can induce short-term weight loss in patients with severe obesity, but usually require specially formulated dietary supplements. Hypocaloric diets are known to induce changes in adipokine secretion, but the influence of a low energy liquid diet (LELD) on the leptin: adiponectin ratio (LAR), a measure of insulin resistance and cardiovascular risk, has not previously been investigated in patients with severe obesity. Bariatric surgery is known to reduce leptin and increase adiponectin levels, but its influence on the leptin: adiponectin ratio (LAR), a measure of insulin sensitivity and cardiovascular risk, has not previously been described. Aim of the first study is to determine the effects of a milk-based meal replacement programme on anthropometric and metabolic characteristics in adults with severe obesity. Aim of the second study is to determine the influence of sleeve gastrectomy on LAR in adults with severe obesity. Aim of the third study is to determine the influence of milk-based meal replacement programme on LAR levels in adults with severe obesity. Methods: First study is a retrospective cohort study of patients attending our hospital-based bariatric medicine service who completed a 24-week program consisting of eight weeks of milk-based meal replacement followed by weight stabilisation and maintenance phases. Second study is a single centre prospective cohort study of adults undergoing laparoscopic sleeve gastrectomy, LAR was measured preoperatively and 12 months after surgery. Third study is single-centre cohort study of adults with severe obesity who completed a 24-week milk-based meal replacement programme, leptin, adiponectin and LAR were measured at the start and on completion of the programme. Results: In the first study of 105 program completers available for follow-up, 53.3% were female. Mean age was 51.1±11.2 years. Body weight decreased from 144.0±27.6 kg at baseline to 121.1±25.0 kg at 24 weeks (P<0.001), a mean total body weight loss of 15.9±6.0 %, with a reduction in body mass index from 50.6±8.0 to 42.6±7.6 kg m-2 (P<0.001). In patients with diabetes, haemoglobin A1c decreased from 66.3±13.0 to 48.3±13.5 mmol/mol (P<0.001) and diabetes medication use decreased significantly. There were significant improvements also in lipid profiles and reductions in antihypertensive medication use. In the second study of 22 patients undergoing sleeve gastrectomy, 17 (12 female, 12 with type 2 diabetes) had follow-up LAR measured at 12.1±1 months. Mean body weight decreased from 130.6±30.8 kg to 97.6±21.6 kg, body mass index (BMI) from 46.9±7.8 to 35.3±7.2 kgm-2 and excess body weight from 87.5±31.3 to 41.3±28.8 % (all p<0.001). The reduction in leptin from 40.7±24.9 to 30.9 ±30.5 ng/ml was not significant (p=0.11), but adiponectin increased from 4.49±1.6 to 8.93±6.36 µg/ml (p=0.005) and LAR decreased from 8.89±4.8 to 5.26±6.52 ng/µg (p=0.001), equivalent to a 70.9% increase in insulin sensitivity. The correlation with the amount of weight lost was stronger for LAR than it was for leptin or adiponectin alone. In the third study of 120 patients who started, 52 (43.3 %) completed the programme. Their mean age was 50.3±11.2 (range 18-74) years, 29 (55.8 %) were female and 20 (38.5 %) had type 2 diabetes mellitus (T2DM). Weight decreased from 148.2±39.6 to 125.4±34.8 kg and BMI decreased from 52.4±11.1 to 44.3±9.8 kgm-2, respectively (all p<0.001). In patients with T2DM, HbA1c decreased from 60.0±17.4 to 47.5±15.5 mmol/mol (p<0.001). Leptin decreased (from 87.2 [48.6, 132.7] to 39.1 [21.0, 76.4] ng/ml) and adiponectin increased (from 5.6 [4.5, 7.5] to 7.1 [5.5, 8.5] µg/ml), with a reduction in LAR from 15 [8.4, 22.4] to 5.7 [3.0, 9.1] ng/µg (all p<0.001), indicating decreased insulin resistance. The percentage weight lost was associated with the percentage reduction in LAR (ß=2.9 [1.7, 4.1], p<0.001) and this association was stronger in patients with T2DM. Conclusion: In the first study, preliminary findings suggest that completion of a 24-week milk-based meal replacement program has large effects on important outcomes in adults with severe obesity. However, attrition was high. Prospective assessment of the efficacy, safety, durability and cost-effectiveness of this intervention seems warranted. In the second study, patients undergoing laparoscopic sleeve gastrectomy had a substantial reduction in their LAR after 12 months, consistent with increased insulin sensitivity and reduced cardiovascular risk, which was proportional to the amount of weight lost. In the third study, patients with severe obesity who completed a milk-based LELD had a substantial reduction in LAR, consistent with decreased insulin resistance and cardiovascular risk, proportional to weight loss.
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NUI Galway