Diabetes is a public health problem of epidemic proportions. It adversely affects morbidity, mortality, and overall healthcare costs. It is well known that frequent self-monitoring of blood glucose (SMBG) and good glycemic control can improve both cost and outcome. SMBG is not adequately embraced because current technology is painful, requires blood, and can be costly. Thus there is an urgent need for a noninvasive blood glucometer that removes all of the impediments to optimal SMBG. Grove Instruments (GI, formerly VivaScan) has developed noninvasive glucose measurement technology that can meet the needs of the burgeoning diabetes population. GI's noninvasive blood glucometer is based on real-time measurements of near-infrared (NIR) light absorption by glucose in blood using a patented Optical Bridget (OB) method. Previous SBIR grants and private company funds have enabled GI to develop and clinically test an advanced engineering prototype handheld noninvasive blood glucometer. Grove's current objective is to develop our NIR transflectance fingertip prototype instrument into a personal handheld noninvasive glucometer ready for commercialization. To achieve this goal we have these specific aims: we will design, build and test 1) a next generation fiberless optical measurement head that is insensitive to alignment of laser diodes and other optical components and is mass-manufacturable at low cost 2) a new ergonomic finger port that provides for physiologic positioning, stability and maximal perfusion, and 3) electronic and mechanical modules to achieve 50% size reduction. Other important aims include: 1) development of a detailed and sophisticated understanding of the microcirculatory capillary arcades to refine detection and quantification of microcirculatory blood volume variation patterns during measurement; 2) develop a new method to precisely measure plasma volume variation during fingertip reperfusion; 3) develop advanced signal processing and feature extraction techniques to improve glucose measurement precision and repeatability, and 4) perform pilot clinical studies and determine the performance accuracy and repeatability of the new (GI210) device. The proposed device has dramatic implications for the quality of glucose control for diabetic persons, their quality of life and longevity. Optimizing SMBG with the GI noninvasive fingertip glucometer can lead to improved clinical outcomes and substantial cost savings to the diabetic individual and to the entire health care system.