The early management of type 2 diabetes usually consists of education related to lifestyle changes especially as 80 to 90% of people with type 2 diabetes are obese. Obesity worsens the metabolic and physiological abnormalities associated with diabetes particularly hyperglycaemia (raised blood sugar), hyperlipidaemia (raised fats in the blood), and hypertension which are prerequisites for macrovascular complications. On the other hand, weight loss is one of the cornerstones of diabetes management as it improves glycaemic (blood glucose) control, lowers triglycerides (a fat in the blood) and low-density lipoprotein cholesterol (the "bad" form of cholesterol) levels and improves blood pressure, mental health and quality of life.
In 1993 the investigators established a structured education programme for patients with new onset type 2 diabetes; following the diagnosis being made in primary care individuals are seen within one week at a nurse led, open-access programme. Since 1994, there has been a 2.5 fold increase in the number of patients diagnosed with type 2 diabetes in our area. At diagnosis, Body Mass Index (BMI) has risen from 28.5 to 31.1kg/m2 associated with a fall in HbA1c (a blood test which gives a measure of long term control of diabetes) levels from 10.3% to 8.1% at presentation. The lower HbA1c at diagnosis probably reflects earlier detection and awareness of the condition. Since 2006, responsibility for providing the education has been transferred to primary care.
More recently, a secondary care based dietitian led group weight management programme comprising more intensive education sessions and regular phone contact was piloted in this unit. A recent evaluation of this service of fifty one overweight and obese individuals who completed the 3-month programme. Average weight loss at 3 months was 4.8 kg equivalent to 4.5 % baseline body weight. Follow up at six months, without further intervention, showed that this was maintained (weight loss 5.8 kg, equivalent to 5.3 %, ns compared to 3/12). 43% of participants achieved \>5% weight reduction with 6% achieving \>10%. The intervention resulted in significant reduction in waistline circumferences, body fat mass, total cholesterol, HbA1c, fasting blood glucose, and blood pressure.
A number of neuro-endocrine factors (hormones that influences the activity of the brain or nervous system) have a role in the control of insulin secretion and in the regulation of food intake. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, the name based on the observation that the insulin response to an oral glucose load was greater than that following the intravenous administration of an equivalent amount of glucose. Incretin hormones are secreted from the small intestine in response to the presence of nutrients in the intestinal lumen. Physiologically, GLP-1 enhances glucose-mediated insulin secretion and suppresses glucagon (a hormone that opposes the action of insulin) secretion. GLP-1 also induces satiety and improves gastric emptying. In studies of patients with established diabetes, GLP-1 levels and the response to oral glucose have been shown to be attenuated and administration of GLP-1 has normalized both fasting and post-prandial glucose levels. It remains uncertain whether lower GLP-1 levels in established diabetes contribute to the pathogenesis of the condition or are a consequence of chronic hyperglycaemia, though the observation that GLP-1 levels are lower in obese subjects suggests the possibility that the former may be the case.
Recently, the investigators measured GLP-1 levels in patients with newly diagnosed type 2 diabetes to assess the effect of an initial period of lifestyle and dietary adjustment. In this pilot project 9 newly diagnosed patients (time from diagnosis 25 + 5 days, 4 female with mean BMI 27.6 kg/m2 were compared with 9 age, gender and body weight matched controls. All participants had a 75g oral glucose tolerance test with measurements of glucose, insulin, GLP-1 and glucagon with the diabetic patients having a repeat OGTT after 3 months. Compared with controls, diabetic patients had higher glucagon levels, lower active GLP-1 at baseline before the glucose load although AUC levels were not significantly different. After 3 months lifestyle adjustment, 5 patients had achieved weight loss (0.2 to 5 kg) but 4 had gained weight (2.7 to 6.5 kg), giving an average weight change for the group of 0.8 Kg. A small change in HbA1c was observed (7.31% vs 6.96%, p=0.25). The levels of active GLP-1 were augmented in the diabetic group accompanied by an increase in the insulin response at 30 mins. though glucagon levels were unaltered.
It is unclear whether more intensive lifestyle changes would result in greater improvements in GLP-1 production and thus greater improvements in diabetic control. If GLP-1 production can be enhanced early following diagnosis of diabetes, this may have favorable consequences for the patient, as GLP-1 has been shown in animal studies and in vitro, to have a role in the regulation of beta glucose sensing and proliferation of beta-cells.
A number of other neuroendocrine peptides have regulatory roles in energy homeostasis and may influence insulin secretion and glycaemic control. Leptin is a protein hormone produced by adipose (fat) tissue which has a key role in regulating energy intake and expenditure, a suppressive effect on appetite and an increase in metabolism. Circulating leptin levels reflect body fat mass. Leptin can enter the the Central Nervous System (CNS) at and interact with centres in the regulation of appetite and metabolism. Despite these suppressive effects, elevated levels have often been noted in obesity, possibly suggesting resistance to the hormone, though may be a result of stimulation by increased insulin levels, which would be expected in obesity. Leptin in turn can inhibit insulin release so a fall in leptin resulting from weight loss may enhance insulin production and may therefore be beneficial in patients with diabetes.
Unlike leptin, ghrelin is an orixigenic (stimulates appetite) hormone which acts via the Growth Hormone secretagogue receptor. It is the only hormone known to stimulate increased feeding and weight gain. Basal plasma levels are increased in malnutrition and decreased in obesity. In some, but not all studies, insulin has been shown to be an inhibitor of ghrelin release. An anticipated rise in ghrelin with weight reduction might offset the effects of lifestyle intervention through stimulation of appetite and increased intake.
Adiponectin is an adipocyte (fat cell) hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism, and may have a role in the metabolic derangements of type 2 diabetes. Though produced in adipose (fat) tissue, plasma adiponectin levels are decreased in obesity as a consequence of down regulation. Adiponectin has insulin sensitizing effects and has central effects on energy homeostasis, promoting weight reduction. Levels of adiponectin have been found to be reduced in type 2 diabetes compared with non-diabetic controls. Weight reduction can increase circulating levels. Again little is known about the effect of changes in adiponectin in the early stages of type 2 diabetes.
