1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...

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Optimal metabolic control, especially early intensive glycemic control, plays a role
in the prevention of progressive beta-cell dysfunction and possibly destruction of the beta-
cells with worsening of diabetes. Many reports have shown that induction of
normoglycemia in DM2 results in both improved beta-cell function and insulin resistance
(90, 91). Rarely, however, has a prolonged benefit been demonstratedwith virtually all
patients becoming hyperglycemic again after a few weeks (92, 93). Until recently it was
unknown whether such outcomes pertained to new-onset DM 2, although patients having
failed diet therapy may show a good response to a short period of intensive insulin therapy
by continuous subcutaneous insulin infusion :CSII (94). Ryan et al (84) recently reported
that, in 16 severe (mean fasting plasma glucose of 239 mg/dl) newly diagnosed DM2
patients, a 2 to 3 weeks` course of intensive insulin therapy by multiple daily insulin
injection (NPH + regular) was able to maintain good glycemic control at 1 year in 7 of the
subjects on diet therapy alone, whilst 8 required oral hypoglycemic agent and 1 required
insulin therapy. The distinguishing features of those who did not require oral agents or
insulin treatment were that they required less insulin during the active insulin therapy phase
(0.37±0.05 vs. 0.73±0.07 units/kg/day) and were able to attain a lower fasting serum
glucose at the end of the period of insulin therapy (106±5 vs. 139±7 mg/dl) . It is
interesting to highlight that the majority of the study patients (15/16) had an evident
recovery of the AUC insulin (oral glucose tolerance test) after the end of insulin therapy,
being dramatically higher than study entry values associated with a significant reduction in
AUC glucose by year end, probably related to the correction of gluco- and lipotoxicity
(significant reduction in triglycerides and FFAs). Thus, the potential benefits of early,
aggressive intervention with insulin therapy to counter both beta-cell dysfunction (and
insulin resistance) must be considered: effects of insulin therapy against chronic
hyperglycemia and lipotoxicity-induced apoptosis of the beta-cells.
In a similar study (85), 138 newly diagnosed DM2s with fasting glucose >200 mg/dl
were hospitalized and treated with CSII for 2 weeks.After CSII the patients were followed
longitudinally on diet alone. Optimal glucose control was achieved within 6.3±3.9 days in
126 patients. The remission rates (percentage of individuals maintaining near euglycemia)
at the third, sixth, twelfth and twenty fourth month were 72.6, 67.0, 47.1 and 42.3%,
respectively. Patients who maintained glycemic control > 12 months (remission group) had