This proof-of-concept study results demonstrated that Oralin could be used as meal insulin in place of mealtime-insulin injections in subjects with type 2 diabetes to regulate the postprandial glucose levels.

The aim of this study was to determine the metabolic effect and the safety of a novel oral insulin spray (Oralin) formulation at breakfast-time in subjects with type 2 diabetes with suboptimal glucose control and maintained on a combination therapy of oral hypoglycemic agents (OHAs). This was an open-label, crossover, randomized study design in subjects (n = 21) with type 2 diabetes (glycated hemoglobin A1c >8.0%). Subjects received each of the following treatments, in random order: metformin + glyburide and placebo puffs at time 0 min; or metformin + glyburide and Oralin spray (100 U) at time 0 min. Fifteen minutes later, subjects were given a standard breakfast containing 360 calories [Sustacal (Mead Johnson, Evansville, IN) liquid meal]. Blood samples were taken at regular intervals to measure serum glucose, insulin, and C-peptide. Time-averaged postprandial glucose increments (PPGIs) between 0 and 240 min were calculated for each treatment. Group mean PPGIs to OHAs versus Oralin in combination with OHAs were compared to determine the mean efficacy of the active treatment. The Oralin spray lowered the 2-h postprandial glucose rise significantly in comparison with the OHAs alone. The serum insulin levels were significantly higher with faster onset of action in the Oralin spray treatment when compared with the OHAs treatment. The reductions in C-peptides were also significantly greater in the Oralin arm than in the OHAs treatment. This study results demonstrated that Oralin could be used as meal insulin as an add-on therapy in combination with failing OHAs treatment in subjects with type 2 diabetes to regulate postprandial glucose levels.

Regular insulin and Oral-lyn had similar glucodynamic effects in subjects with T1DM receiving twice-daily insulin analogue as baseline therapy. Intensive monitoring and timely corrections with additional snacks, additional sc regular insulin, or Oral-lyn puffs resulted in appropriate glycemic control as assessed by individual daily glycemic responses and, especially, normal preprandial glycemia. Protein glycation decreased, but not significantly.

Objective: To describe the clinical and biochemical features, and perform molecular analysis for candidate abnormalities in a novel familial syndrome of intrauterine growth retardation (IUGR), failure of an adolescent growth spurt with proportional adult short stature, minimal subluxation of the 5th metacarpal-phalangeal joint, and adult-onset insulin-resistant diabetes unrelated to obesity or other manifestations of metabolic syndrome (MS). Design: Detailed clinical history, auxological, biochemical, radiological, and molecular studies, including DNA analysis and in vitro study of the GH/IGF1 pathway. Materials and methods: Ten affected adults from two generations of five related families were studied in detail, and information obtained about nine other likely affected individuals. Results: Height Z-scores ranged from K7.3 to K3.8. Unaffected parents of the older generation and frequency of confirmed and suspected instances of the syndrome in the two generations studied is consistent with autosomal recessive inheritance. Insulin resistance was uniformly present in seven subjects tested who were not taking insulin. Diabetes severity did not correlate with overweight. Subjects did not have other typical manifestations of MS such as substantial hyperlipidemia, osteoporosis, or hypertension. No biochemical abnormality in the GH/IGF1 axis or molecular defect was found. Conclusions: While the association of IUGR and adult MS, including diabetes, has been well documented, these subjects did not have typical manifestations of MS. Abnormalities in common components that could result in a combination of IUGR, severe postnatal growth, and insulin resistance have been ruled out. A mutation in an unidentified gene may affect intrauterine and postnatal growth, with insulin resistance directly affected or as a result of this growth phenomenon.

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