Patrick J. English

Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes

BACKGROUND There is evidence that reducing blood glucose concentrations, inducing weight loss, and improving the lipid profile reduces cardiovascular risk in people with type 2 diabetes. OBJECTIVE We assessed the effect of various diets on glycemic control, lipids, and weight loss. DESIGN We conducted searches of PubMed, Embase, and Google Scholar to August 2011. We included randomized controlled trials (RCTs) with interventions that lasted ≥6 mo that compared low-carbohydrate, vegetarian, vegan, low-glycemic index (GI), high-fiber, Mediterranean, and high-protein diets with control diets including low-fat, high-GI, American Diabetes Association, European Association for the Study of Diabetes, and low-protein diets. RESULTS A total of 20 RCTs were included (n = 3073 included in final analyses across 3460 randomly assigned individuals). The low-carbohydrate, low-GI, Mediterranean, and high-protein diets all led to a greater improvement in glycemic control [glycated hemoglobin reductions of -0.12% (P = 0.04), -0.14% (P = 0.008), -0.47% (P < 0.00001), and -0.28% (P < 0.00001), respectively] compared with their respective control diets, with the largest effect size seen in the Mediterranean diet. Low-carbohydrate and Mediterranean diets led to greater weight loss [-0.69 kg (P = 0.21) and -1.84 kg (P < 0.00001), respectively], with an increase in HDL seen in all diets except the high-protein diet. CONCLUSION Low-carbohydrate, low-GI, Mediterranean, and high-protein diets are effective in improving various markers of cardiovascular risk in people with diabetes and should be considered in the overall strategy of diabetes management.

The relationship of ghrelin to biochemical and anthropometric markers of adult growth hormone deficiency

introduction  Ghrelin is the natural ligand of the growth hormone secretagogue receptor (GHS‐R) and potently stimulates GH release in humans. Ghrelin is found in the hypothalamus, but most circulating ghrelin is derived from the stomach. Ghrelin stimulates food intake but circulating levels are low in obesity. We hypothesized that GH deficiency (GHD) might be associated with increased circulating ghrelin concentrations as a result of low GH levels. We therefore measured circulating ghrelin concentrations, leptin and body composition in subjects with GHD and healthy controls.

Ghrelin restores 'lean-type' hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects

Objective:To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects.Design:A randomized, double-blind, placebo-controlled study.Patients:Nine lean subjects (mean body mass index (BMI) 23.5±3 kg/m2) and nine morbidly obese subjects (mean BMI 51.4±10 kg/m2) and eight postgastrectomy subjects (mean BMI 22.4±1.0 kg/m2).Interventions:Subjects were infused with either intravenous ghrelin (5 pmol kg−1 min−1) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion.Main outcome measures:Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry.Results:Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P<0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a ‘lean-type’ pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P<0.001).Conclusions:Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.

Metformin prolongs the postprandial fall in plasma ghrelin concentrations in type 2 diabetes

Weight loss is difficult to achieve in type 2 diabetes and many therapies are associated with weight gain, an effect attenuated by metformin. We studied the effects of metformin on energy expenditure, appetite and the regulation of PYY and ghrelin in type 2 diabetes.

Fasting plasma peptide-YY concentrations are elevated but do not rise postprandially in type 2 diabetes

To the Editor: Weight loss appears to be particularly difficult to achieve in patients with type 2 diabetes compared to their non-diabetic counterparts [1]. The hormones peptide YY3–36 (PYY) and ghrelin are implicated in the regulation of appetite, energy balance and the pathophysiology of obesity. PYY is released from L-cells in the gut in response to food [2]. Fasting concentrations are lower and postprandial responses attenuated in obese subjects [3], and infusions of PYY to mimic the postprandial concentrations found in lean subjects reduce appetite and food intake in obese subjects [3, 4], suggesting a potential role in the pathogenesis of obesity. Peripheral administration of ghrelin increases food ingestion [5, 6], and prolonged administration leads to obesity [5, 7]. Circulating ghrelin shows preprandial peaks and postprandial troughs suggesting a role in meal initiation. Against this background, we sought to determine whether type 2 diabetes, independent of obesity status, affected the prandial regulation of PYY and ghrelin in a manner that would explain both the predisposition to increased energy intake and weight gain, and the difficulties in achieving weight loss seen in type 2 diabetes. The study was approved by the local ethics committee and subjects, who were volunteers, gave written informed consent. We studied 11 subjects with diet-controlled type 2 diabetes and 16 control subjects of similar age, sex and BMI. All subjects with diabetes were free from complications and had an HbA1c <10%. Urea, electrolytes, full blood count, thyroid function and resting electrocardiogram were normal in all subjects. Antihypertensive, lipid-lowering and aspirin treatment were not considered exclusion criteria unless they included beta-adrenoreceptor antagonists. Subjects attended at 08.30 h, having fasted from 22.00 h the previous evening and refrained from alcohol or strenuous physical activity for at least 24 h and cigarettes for at least 12 h. Anthropometric variables were measured and body fat percentage estimated using whole-body bioelectrical impedance analysis (Tanita Systems, Stokie, IL, USA). Studies were conducted at an ambient temperature of 22±1°C. Following baseline blood samples, subjects consumed a standard mixed meal of 600 kcal (63.9% carbohydrate, 13.0% protein, 23.1% fat) over 20 min. Blood was collected at 15, 30, 60, 120, 180, 240, 300 and 360 min after the meal. Samples were centrifuged, frozen immediately and stored at −80°C until assayed. Plasma PYY-like immunoreactivity (specifically PYY3–36 and PYY1–36 with no cross-reactivity with other peptides) was measured using an established radioimmunoassay [2]. Ghrelin-like immunoreactivity was measured with a specific and sensitive Diabetologia (2006) 49:2219–2221 DOI 10.1007/s00125-006-0344-y

Ghrelin does not orchestrate the metabolic changes seen in fasting but has significant effects on lipid mobilisation and substrate utilisation

OBJECTIVE Short-term fasting is associated with increased GH pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelins role during fasting and the effects of exogenous ghrelin on lipid mobilisation. DESIGN Randomised placebo-controlled study. METHODS In this study, ten controls (body mass index (BMI) 23.3±3.2), ten morbidly obese subjects (BMI 50.1±10.6) and six post-gastrectomy subjects (BMI 25.2±1.0) were fasted for 36  h undergoing regular blood sampling. On a separate occasion, subjects were infused with either i.v. ghrelin (5  pmol/kg per min) or saline over 270  min. RESULTS Obese and post-gastrectomy subjects had lower ghrelin compared with controls (ANOVA, P=0.02) during the fast. Controls and gastrectomy subjects showed a similar increase in GH pulsatility, circulating non-esterified fatty acids (NEFA) and 3β-hydroxybutyrate (3 HB). Obese subjects had an impaired GH response (P<0.001), reduced excursions of 3 HB (P=0.01) but no change in NEFA excursions (P=0.09) compared with controls. Ghrelin infusion increased GH, NEFA and ketone bodies (ANOVA, P<0.0001) in all the three groups, but GH response was impaired in the obese subjects (P=0.001). Ghrelin also induced a significant (ANOVA, P=0.004) biphasic NEFA response to meals in all the subjects. CONCLUSIONS Despite low circulating ghrelin, gastrectomy subjects maintain a normal metabolic response to fasting, implying that ghrelin plays a minimal role. In contrast, infused ghrelin has significant effects on lipid mobilisation and induces a marked biphasic NEFA response to meals. Hence, ghrelin may play a significant role in meal-related substrate utilisation and metabolic flexibility.

Localisation of an occult thyrotropinoma with

1 somatostatin analogue therapy 2 3 Olympia Koulouri, Andrew C Hoole, Patrick English, Kieren Allinson, Nagui Antoun, Heok Cheow, 4 Neil G Burnet, Neil Donnelly, Richard J Mannion, Mark Gurnell 5 6 1Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, and Departments of 7 2Medical Physics, 4Pathology, 5Neuroradiology, 6Nuclear Medicine, 7Oncology, 8Otolaryngology and 8 9Neurosurgery, University of Cambridge and National Institute for Health Research Cambridge Biomedical 9 Research Centre, Addenbrooke’s Hospital, Cambridge, UK. 3Department of Diabetes and Endocrinology, 10 Derriford Hospital, Plymouth, UK. 11

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Dietary modification is a crucial aspect of preventing and managing pre-existing type 2 diabetes. Current guidelines recommend diets high in carbohydrate and low in fat for people with type 2 diabetes; however, it is clear that weight loss from energy restriction is effective in preventing diabetes and improving glycemic control. Although there is limited evidence for the most effective dietary approach a Mediterranean style diet should be considered as an effective strategy in the prevention and treatment of type 2 diabetes. Contrary to accepted recommendations there is an observed association of low intake of saturated, trans fat and simple sugars with an increased incidence of type 2 diabetes while diets high in unsaturated fat and fiber appear to be protective.