Endocrinol Metab 1999 13 279-294.

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uated intravenous, subcutaneous (both Regular and fast-acting), and inhaled insulin. Heinemann et al. demonstrated in 1997 that the relative effectiveness of inhaled insulin was approximately 10% with regard to intravenous insulin administration and 8% with regard to subcutaneous insulin administration. In addition, Heise et al. reported that the onset of action of inhaled insulin appears to be more rapid than that of subcutaneous insulin. Inhaled insulin demonstrated a faster onset of action than subcutaneous Regular insulin and even insulin lispro (early ti0%: 32, 48, and 40 minutes, respectively). The maximal metabolic action (based on glucose infusion rates) was comparable with that of Regular insulin and lower than that of lispro. The duration of action of inhaled insulin (late ts was between that of lispro and Regular insulin (382, 309, and 413 minutes, respectively) (Figure 2). In addition to the above, it appears from several other evaluations that the pharmacokinetic and pharmacodynamic profiles of pulmonary delivery of insulin mimic those of the normal physiological response.

Clinical Results with Inhaled Insulin

On a clinical level, however, studies have suggested that inhaled insulin may be effective in both type I and type 2 subjects who are taking insulin and is effective in type 2 diabetic patients failing on oral agents. In 1999, Weiss et al. examined the effect of adding inhaled insulin (using a dry-powder formulation) to oral

agents in a study in 69 patients with poorly controlled type 2 diabetes (HbA 8.1 -11.9% despite receiving therapeutic doses of a sulfonylurea and/or metformin). Patients were randomized to either continue with their current oral agent alone or take the oral agent in combination with inhaled insulin (one or two inhalations three times daily, i.e., before meals). Inhaled insulin treatment was observed to significantly improve HbA,c in subjects receiving inhaled insulin compared with the level in those receiving an oral agent alone (—2.28 vs. —0.06%, respectively; p < 0.001). Inhaled insulin therapy was well tolerated, with only one report of severe hypoglycemia. In addition, pulmonary function tests remained Stable over the 3-month study period.

Two phase 2 studies have been reported on clinical use of the dry-powder formulation for treatment of type I and 2 diabetic subjects who were on insulin injections. Skyler et al. recently evaluated 73 patients with type 1 diabetes who received either their usual insulin regimen of two or three injections daily or pre-meal inhaled insulin plus an injection of Ultralente insulin at bedtime, for 12 weeks. At 12 weeks, there was no significant difference in HbAk or fasting or postprandial glucose concentrations between those randomized to inhaled insulin versus those taking subcutaneous insulin. In a study of 26 patients with type 2 diabetes who were receiving insulin therapy prior to study, patients were administered one or two inhalations of the dry-powder insulin formulation (between 3 and 18 units, according to the glucose response) before each meal plus bedtime Ultralente insulin. Insulin doses were adjusted at weekly intervals to achieve the target preprandial glucose of 100-160 mg/dl. Mean HbAlc levels were observed to significantly decrease by 0.71% when compared with the baseline value. The limitation of both the type 1 and 2 studies of inhaled insulin versus subcutaneous insulin is that they were of open-label design. Nevertheless, these studies strongly suggested that inhaled insulin may be a viable option for patients with either type 1 or type 2 diabetes currently on insulin therapy.

An important component of the early inhaled-insulin protocols is that patients appeared to be very satisfied with inhaled-insulin treatment. Patient-satisfaction surveys have confirmed that, after I year of treatment, patients receiving inhaled dry-powder Insulin maintained their satisfaction with significantly greater improvements than those using conventional insulin injections, in global satisfaction and convenience/ease of use. Gerber et al. found that patients who switched from subcutaneous insulin to inhaled insulin showed a significant improvement (p < 0.05) in global satisfaction (20% improvement), convenience/ease of use (28% improvement), and social stigma (16% improvement). In contrast, patients who switched from inhaled to subcutaneous insulin showed a trend toward worsening satisfaction. Thus, adherence to treatment with inhaled insulin may be better than that observed with injection regimens, although this must await confirmation by long-term studies.

SUMMARY

It is now unquestioned that glycemic control is required lo prevent progression of diabetic complications. This has been firmly established not only for type 1 diabetes but also for type 2 diabetes. Insulin is the only treatment for type 1. and the natural history of type 2 diabetes suggests that insulin may be required for it too, given the progressive nature of the disease. Thus, regardless of the type of diabetes, multiple injection therapy may be required to adequately control glucose levels. Unfortunately, a number of barriers exist at both the patient and physician levels that may prevent the advancement to intensive insulin therapy. In addition to other relevant concerns, one obstacle is that injection remains the only viable means of administering insulin. However, numerous approaches have been evaluated to administer insulin noninvasively. Although the research is still very active in this area, pulmonary delivery, at this date, appears to have the most potential to become a clinically viable alternative to insulin injections. The clinical evidence shows that inhaled insulin is effective and well tolerated. It has a more physiological insulin profile than conventional subcutaneous insulin making it ideal for preprandial administration. Inhaled insulin, in the early studies, has met with increased patient satisfaction. The additional studies needed to confirm long-term efficacy and long-term pulmonary safety are underway. However, the evidence to date suggests that pulmonary insulin delivery may offer the potential to improve compliance and thereby help reduce the number of complications associated with diabetes.

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Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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