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

Abstract

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