Symposium
The link between obesity and diabetes
Jennifer B. Marks
Miami, FL, USA
A symposium chaired by Dr Michael W. Schwartz, highlighting
potential connections between the pathogenetic mechanisms underlying
Type 2 diabetes and obesity, was entitled “Obesity and Diabetes: The
Odd Couple”.
Paradox
The theme of the session was to explore the apparent paradox between
these two commonly co-existing conditions. That paradox is: since
elevated insulin levels are associated with obesity, and decreased or
deficient insulin secretion is associated with the clinical development
of diabetes, how do we explain the occurrence of both in the same
individual? While the insulin resistance and hyperinsulinemia related to
obesity are certainly one potential explanation, the symposium’s first
presenter, Dr Daniel Porte, Jr, focused on the possible primary
role of the beta-cell in the link between diabetes and obesity,
presenting data that insulin (and insulin deficiency) is (are) a key
mediator of adiposity through CNS effects. His hypothesis develops first
from the fact that, while insulin-resistant individuals tend to become
more insulin-resistant over time, not all develop diabetes. In fact,
only those whose islets fail develop diabetes. Dr Porte points to a
decrease in the processing of proinsulin (hyperproinsulinemia) which
results in an increased deposition of amyloid in the islets as potential
mechanisms which lead to apoptosis of beta-cells, and resultant islet
failure.
Figure: Insulin modulates appetite via
effects on increasing Neuropeptide Y(NPY), a potent anorexogenic substance.
Insulin deficiency results in a decrease in NPY, resulting in increased
food intake and adiposity.
He further discusses evidence that insulin has direct CNS effects
resulting in appetite suppression probably via stimulatory effects on
neuropeptide Y, a potent anorexogenic substance. Therefore, the unifying
link between diabetes and obesity could lie in beta-cell failure and may
be explained thus: as beta-cells fail to secrete adequate insulin to
overcome insulin resistance, which results from a combination of genetic
and environmental factors, hyperglycemia develops. Body adiposity
increases when insulin secretion is impaired and insulin action is
reduced in the CNS. In fact, there is evidence in some populations,
Japanese men for example, that an impairment in insulin secretion is
present up to 5 years before the presence of intraabdominal fat, a
powerful predictor of insulin resistance in this population. Whether
this hypothesis explains the sequence of events leading to the
development of diabetes in most populations who develop diabetes is
controversial. Many investigators still believe that insulin resistance
precedes beta-cell failure in many, if not most, individuals with Type 2
diabetes, and in the obese population, at least, beta-cell failure is a
result of the inevitable inability of the beta-cell to adequately
compensate for this resistance. It may prove, however, that beta cell
failure preceeding obesity and insulin resistance may represent one
sequence of events in the development of this most heterogeneous
disease, diabetes. If this hypothesis is correct in some cases of type 2
diabetes development, an unanswered question begs explanation: why are
the effects of insulin deficiency on body adiposity different in Type 1 diabetes?
