This protocol is for study of the effect of inhibition of parasympathetic outflow on insulin secretion and glucose metabolism. Insulin secretion will be measured during infusions of escalating doses of atropine. Other clinical parameters of parasympathetic inhibition by atropine will also be assessed.

Children of mothers who had diabetes during pregnancy are at an increased risk of diabetes and obesity in later life, effects partly mediated by the early environment experienced by the offspring of diabetic mothers in utero. In this protocol, we address why intra-uterine exposure to maternal diabetes might lead to later childhood obesity. Previous studies of children of diabetic mothers have not detected any alteration in energy expenditure, either as resting metabolic rate or physical activity. We will now examine whether they are at an increased risk of obesity due to differences in food intake. We will assess composition of the diet, patterns of eating, taste preference and physiological responses to a mixed meal. No previous work in human subjects has addressed these issues.

• INCLUSION CRITERIA:

Group 1: Offspring of mothers with diabetes during pregnancy.

Maternal diagnosis of type 2 diabetes (by WHO criteria after a 75g OGTT or on clinical grounds with at least one random plasma glucose greater than 200mg/dl) before or during the index pregnancy.

Group 2: Offspring of mothers with diabetes diagnosed following pregnancy.

Maternal diagnosis of type 2 diabetes (by WHO criteria after a 75g OGTT or on clinical grounds with at least one random plasma glucose greater than 200 mg/dl) after the index pregnancy.

It is important to also ensure that these mothers did not have any major disturbance in glucose tolerance during the index pregnancy and a record of normal glucose tolerance after the index pregnancy; therefore they will only be included if there are also:

Adequate records of glucose testing during the index pregnancy and these records are not in keeping with a diagnosis of gestational diabetes (by either WHO criteria if a 75g oral glucose tolerance test has been carried out).

At least one non-diabetic OGTT after the index pregnancy.

EXCLUSION CRITERIA:

1. History of weight loss for child (greater than 2kg over last 6 months).
2. Presence of other major illnesses which might interfere with appetite or food intake in mother or child.
3. Child not living with mother.