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Weight Gain, Obesity and Type 2 Diabetes
Association Between Body Weight, Diabetes and Insulin Secretion
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Weight Gain & Type 2 Diabetes

Diabetes & Obesity
Type 2 diabetes is strongly associated with obesity. This is true of populations such as the Pima Indians and some Polynesian groups moving from subsistence to plenty, but it is also true of western society generally. Obesity is not, however, sufficient by itself to cause type 2 diabetes. The sub set of the population that succumb clearly have genetic traits as well as the environmental trigger. There is little that we can do about the population gene traits and much that we could potentially do about food consumption and exercise. The problem is turning that potential into practice.

Weight Gain & Insulin
The situation at the onset of type 2 diabetes then is that much of the battle for optimizing habits such as regular exercise and healthy eating has already been lost. In clinical practice we have failed spectacularly to change behavior after diagnosis towards exercise regimens and eating habits that have the potential to reverse the pathology. Middle aged overweight people do not, and maybe cannot, take up enough exercise to influence the process and eating habits are socially and habitually ingrained. Therapies which increase insulin secretion are generally associated with progressive weight gain, though we do not have enough data before diagnosis to be certain as to whether this is a continuing trend in body mass. Certainly the UKPDS showed a weight gain of a median 4 kg in such people.

Weight Gain & Metformin
Weight increase was much improved in those treated less intensively for their glycemia and interestingly in those given metformin. Those overweight subjects who were on metformin had improved glycemia without a large weight increase and it may be this specific combination that caused the best benefit for tissue damage outcome in type 2 diabetes. However, the UKPDS was clear in its conclusion that of the two evils hypoglycemia was worse than weight increase. With the advent of thiazolidinediones, where weight increases even faster than with insulin or sulphonylurea, we will need to wait for the outcome of clinical trials before deciding whether these agents are suitable for widespread use or whether we should reserve them for specific indications. New agents such as GLP1 analogues now in commercial pipelines may have the potential to control glycemia without weight increase. Certainly this seems to be a finding in primate studies.

Prevention of Weight Gain by Clinical Practice
We know that in specific cases it is possible to stop weight increase or even reverse it but the tragedy is that in general clinical practice we are not achieving such an outcome, and it is likely that the morbidity of diabetes is significantly compounded and exacerbated by obesity.

Source: Dr David Matthews, Diabetes Research Laboratory, Radcliffe Infirmary, Oxford, UK.

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