Mobile multi-configuration clinical translational Raman system for oral cancer application.

Early diagnosis of oral cancer is critical to improve the survival rate of patients. Raman spectroscopy, a non-invasive spectroscopic technique, has shown potential in identifying early-stage oral cancer biomarkers in the oral cavity environment. However, inherently weak signals necessitate highly sensitive detectors, which restricts widespread usage due to high setup costs. In this research, the fabrication and assembly of a customised Raman system that can adapt three different configurations for the in vivo and ex vivo analysis is reported. This novel design will help in reducing the cost required to have multiple Raman instruments specific for a given application. First, we demonstrated the capability of a customized microscope for acquiring Raman signals from a single cell with high signal-to-noise ratio. Generally, when working with liquid samples with low concentration of analytes (such as saliva) under a microscope, excitation light interacts with a small sample volume, which may not be representative of whole sample. To address this issue, we have designed a novel long-path transmission set-up, which was found to be sensitive towards low concentration of analytes in aqueous solution. We further demonstrated that the same Raman system can be incorporated with the multimodal fibre optical probe to collect in vivo data from oral tissues. In summary, this flexible, portable, multi-configuration Raman system has the potential to provide a cost-effective solution for complete screening of precancer oral lesions.

Extended-wavelength diffuse reflectance spectroscopy dataset of animal tissues for bone-related biomedical applications.

Diffuse reflectance spectroscopy (DRS) has been extensively studied in both preclinical and clinical settings for multiple applications, notably as a minimally invasive diagnostic tool for tissue identification and disease delineation. In this study, extended-wavelength DRS (EWDRS) measurements of ex vivo tissues ranging from ultraviolet through visible to the short-wave infrared region (355-1919 nm) are presented in two datasets. The first dataset contains labelled EWDRS measurements collected from bone cement samples and ovine specimens including 10 tissue types commonly encountered in orthopedic surgeries for data curation purposes. The other dataset includes labelled EWDRS measurements of primarily bone structures at different depths during stepwise drilling into intact porcine skulls until plunging into the cranial cavity. The raw data with code for pre-processing and calibration is publicly available for reuse on figshare. The datasets can be utilized not only for exploratory purposes in machine learning model construction, but also for knowledge discovery in the orthopedic domain to identify important features for surgical guidance, extract physiological parameters and provide diagnostic insights.

Miniature, multi-dichroic instrument for measuring the concentration of multiple fluorophores.

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Due to the highly infiltrative nature of glioblastoma multiforme (GBM) and limited intraoperative visualization of the tumour margin, incomplete surgical resection has been observed to occur in up to 80 % of GBM cases, leading to nearly universal tumour recurrence and overall poor prognosis of 14.6 months median survival. This research presents a miniaturized, SiPMT-based optical system for simultaneous measurement of powerful DRS and weak auto-fluorescence for brain tumour detection. The miniaturisation of the optical elements confined the spatial separation of eight select wavelengths into footprint measuring 1.5 × 2 × 16 mm. The small footprint enables this technology to be integrated with existing surgical guidance instruments in the operating room. It's dynamic ability to subtract any background illumination and measure signal intensities across a broad range from pW to mWs make this design much more suitable for clinical environments as compared to spectrometer-based systems with limited dynamic ranges and high integration times. Measurements using optical tissue phantoms containing mixed fluorophores demonstrate correlation coefficients between the fitted response and actual concentration using PLS regression being 0.95, 0.87 and 0.97 for NADH, FAD and PpIX , respectively. These promising results indicate that our proposed miniaturized instrument could serve as an effective alternative in operating rooms, assisting surgeons in identifying brain tumours to achieving positive surgical outcomes for patients.

Promoting the Emergence of Vocational Knowledge through Equivalence-Based Instruction with a Young Adult with Autism.

We sought to evaluate the efficacy of an equivalence-based instructional program to teach vocational information to a young adult. This work has the potential to aid in workplace or vocational programming to teach declarative information about employment settings. We directly reinforced a subset of relations [Employee names (A) to job titles (B) (A-B) and a job titles (B) to a job responsibilities (C) (B-C)] and tested for the untrained emergence of other relations [Employee names (A) to job responsibilities (C) (A-C) and job responsibilities (C) to employee names (A) (C-A)]. In a multiple baseline across employment settings, mastery was observed across trained and derived relations with implications for vocational training. Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-023-00814-z.

Frameworks of wavelength selection in diffuse reflectance spectroscopy for tissue differentiation in orthopedic surgery.

Significance: Wavelength selection from a large diffuse reflectance spectroscopy (DRS) dataset enables removal of spectral multicollinearity and thus leads to improved understanding of the feature domain. Feature selection (FS) frameworks are essential to discover the optimal wavelengths for tissue differentiation in DRS-based measurements, which can facilitate the development of compact multispectral optical systems with suitable illumination wavelengths for clinical translation. Aim: The aim was to develop an FS methodology to determine wavelengths with optimal discriminative power for orthopedic applications, while providing the frameworks for adaptation to other clinical scenarios. Approach: An ensemble framework for FS was developed, validated, and compared with frameworks incorporating conventional algorithms, including principal component analysis (PCA), linear discriminant analysis (LDA), and backward interval partial least squares (biPLS). Results: Via the one-versus-rest binary classification approach, a feature subset of 10 wavelengths was selected from each framework yielding comparable balanced accuracy scores (PCA: 94.8±3.47%, LDA: 98.2±2.02%, biPLS: 95.8±3.04%, and ensemble: 95.8±3.16%) to those of using all features (100%) for cortical bone versus the rest class labels. One hundred percent balanced accuracy scores were generated for bone cement versus the rest. Different feature subsets achieving similar outcomes could be identified due to spectral multicollinearity. Conclusions: Wavelength selection frameworks provide a means to explore domain knowledge and discover important contributors to classification in spectroscopy. The ensemble framework generated a model with improved interpretability and preserved physical interpretation, which serves as the basis to determine illumination wavelengths in optical instrumentation design.

Microcamera Visualisation System to Overcome Specular Reflections for Tissue Imaging.

In vivo tissue imaging is an essential tool for medical diagnosis, surgical guidance, and treatment. However, specular reflections caused by glossy tissue surfaces can significantly degrade image quality and hinder the accuracy of imaging systems. In this work, we further the miniaturisation of specular reflection reduction techniques using micro cameras, which have the potential to act as intra-operative supportive tools for clinicians. In order to remove these specular reflections, two small form factor camera probes, handheld at 10 mm footprint and miniaturisable to 2.3 mm, are developed using different modalities, with line-of-sight to further miniaturisation. (1) The sample is illuminated via multi-flash technique from four different positions, causing a shift in reflections which are then filtered out in a post-processing image reconstruction step. (2) The cross-polarisation technique integrates orthogonal polarisers onto the tip of the illumination fibres and camera, respectively, to filter out the polarisation maintaining reflections. These form part of a portable imaging system that is capable of rapid image acquisition using different illumination wavelengths, and employs techniques that lend themselves well to further footprint reduction. We demonstrate the efficacy of the proposed system with validating experiments on tissue-mimicking phantoms with high surface reflection, as well as on excised human breast tissue. We show that both methods can provide clear and detailed images of tissue structures along with the effective removal of distortion or artefacts caused by specular reflections. Our results suggest that the proposed system can improve the image quality of miniature in vivo tissue imaging systems and reveal underlying feature information at depth, for both human and machine observers, leading to better diagnosis and treatment outcomes.

Association between intrapartum fetal pulse oximetry and adverse perinatal and long-term outcomes: a systematic review and meta-analysis protocol.

Background: Current methods of intrapartum fetal monitoring based on heart rate, increase the rates of operative delivery but do not prevent or accurately detect fetal hypoxic brain injury. There is a need for more accurate methods of intrapartum fetal surveillance that will decrease the incidence of adverse perinatal and long-term neurodevelopmental outcomes while maintaining the lowest possible rate of obstetric intervention. Fetal pulse oximetry (FPO) is a technology that may contribute to improved intrapartum fetal wellbeing evaluation by providing a non-invasive measurement of fetal oxygenation status. Objective: This systematic review and meta-analysis aims to synthesise the evidence examining the association between intrapartum fetal oxygen saturation levels and adverse perinatal and long-term outcomes in the offspring. Methods: We will include randomised control trials (RCTs), cohort, cross-sectional and case-control studies which examine the use of FPO during labour as a means of measuring intrapartum fetal oxygen saturation and assess its effectiveness at detecting adverse perinatal and long-term outcomes compared to existing intrapartum surveillance methods. A detailed systematic search of PubMed, EMBASE, CINAHL, The Cochrane Library, Web of Science, ClinicalTrials.Gov and WHO ICTRP will be conducted following a detailed search strategy until February 2024. Three authors will independently review titles, abstracts and full text of articles. Two reviewers will independently extract data using a pre-defined data extraction form and assess the quality of included studies using the Risk of Bias tool for RCTs and Newcastle-Ottawa Scale for observational studies. The grading of recommendations, assessment, development, and evaluation (GRADE) approach will be used to evaluate the certainty of the evidence. We will use random-effects meta-analysis for each exposure-outcome association to calculate pooled estimates using the generic variance method. This systematic review will follow the Preferred Reporting Items for Systematic reviews and Meta-analyses and MOOSE guidelines. PROSPERO registration: CRD42023457368 (04/09/2023).

Silicon Photomultiplier-A High Dynamic Range, High Sensitivity Sensor for Bio-Photonics Applications.

This work is an overview of silicon photomultipliers (SiPMs) with a view to defining their importance for bio-photonic and clinical applications. SiPMs are benchmarked against other common photodetectors, namely, PIN diodes and avalanche photodetectors (APDs) and are compared with respect to important circuit design parameters. It will be shown that careful selection of the design bias voltage, overvoltage, gain defining components and device integration to micro-optics can allow SiPM detectors to achieve considerable sensitivity for auto-fluorescence (AF) detection and a wide dynamic range at low optical powers (~1 pW to ~4 µW). The SiPM has a manageable bias voltage (~25 V to ~30 V DC) for systems integration, and with optimised sensitivity it will enhance bio-photonic research in the area of AF to detect intraoperatively, for example, brain tumour margins.

Perspective on the integration of optical sensing into orthopedic surgical devices.

SIGNIFICANCE: Orthopedic surgery currently comprises over 1.5 million cases annually in the United States alone and is growing rapidly with aging populations. Emerging optical sensing techniques promise fewer side effects with new, more effective approaches aimed at improving patient outcomes following orthopedic surgery. AIM: The aim of this perspective paper is to outline potential applications where fiberoptic-based approaches can complement ongoing development of minimally invasive surgical procedures for use in orthopedic applications. APPROACH: Several procedures involving orthopedic and spinal surgery, along with the clinical challenge associated with each, are considered. The current and potential applications of optical sensing within these procedures are discussed and future opportunities, challenges, and competing technologies are presented for each surgical application. RESULTS: Strong research efforts involving sensor miniaturization and integration of optics into existing surgical devices, including K-wires and cranial perforators, provided the impetus for this perspective analysis. These advances have made it possible to envision a next-generation set of devices that can be rigorously evaluated in controlled clinical trials to become routine tools for orthopedic surgery. CONCLUSIONS: Integration of optical devices into surgical drills and burrs to discern bone/tissue interfaces could be used to reduce complication rates across a spectrum of orthopedic surgery procedures or to aid less-experienced surgeons in complex techniques, such as laminoplasty or osteotomy. These developments present both opportunities and challenges for the biomedical optics community.

Label-Free Optical Spectroscopy for Early Detection of Oral Cancer.

Oral cancer is the 16th most common cancer worldwide. It commonly arises from painless white or red plaques within the oral cavity. Clinical outcome is highly related to the stage when diagnosed. However, early diagnosis is complex owing to the impracticality of biopsying every potentially premalignant intraoral lesion. Therefore, there is a need to develop a non-invasive cost-effective diagnostic technique to differentiate non-malignant and early-stage malignant lesions. Optical spectroscopy may provide an appropriate solution to facilitate early detection of these lesions. It has many advantages over traditional approaches including cost, speed, objectivity, sensitivity, painlessness, and ease-of use in clinical setting for real-time diagnosis. This review consists of a comprehensive overview of optical spectroscopy for oral cancer diagnosis, epidemiology, and recent improvements in this field for diagnostic purposes. It summarizes major developments in label-free optical spectroscopy, including Raman, fluorescence, and diffuse reflectance spectroscopy during recent years. Among the wide range of optical techniques available, we chose these three for this review because they have the ability to provide biochemical information and show great potential for real-time deep-tissue point-based in vivo analysis. This review also highlights the importance of saliva-based potential biomarkers for non-invasive early-stage diagnosis. It concludes with the discussion on the scope of development and future demands from a clinical point of view.

Effect of the presence of amniotic fluid for optical transabdominal fetal monitoring using Monte Carlo simulations.

About a third of babies are delivered by Cesarean section. There has been an increase in maternal deaths during labor due to complications with subsequent births after a C-section. Therefore, there is a clinical motivation to reduce the C-section rate. Current techniques are, however, inefficient at determining fetal distress leading to a high false positive rate for complications and ultimately a C-section. For the current study, Monte Carlo simulations were used to calculate the amount of signal received on a model of a pregnant mother, as well as, the percent of the signal that comes from the fetal layer. Models with and without a 1 mm amniotic fluid were compared and showed differing trends.

Combined autofluorescence and diffuse reflectance for brain tumour surgical guidance: initial ex vivo study results.

This ex vivo study was conducted to assess the potential of using a fibre optic probe system based on autofluorescence and diffuse reflectance for tissue differentiation in the brain. A total of 180 optical measurements were acquired from 28 brain specimens (five patients) with eight excitation and emission wavelengths spanning from 300 to 700 nm. Partial least square-linear discriminant analysis (PLS-LDA) was used for tissue discrimination. Leave-one-out cross validation (LOOCV) was then used to evaluate the performance of the classification model. Grey matter was differentiated from tumour tissue with sensitivity of 89.3% and specificity of 92.5%. The variable importance in projection (VIP) derived from the PLS regression was applied to wavelengths selection, and identified the biochemical sources of the detected signals. The initial results of the study were promising and point the way towards a cost-effective, miniaturized hand-held probe for real time and label-free surgical guidance.

Cranial Perforation Using an Optically-Enhanced Surgical Drill.

The design of mechanically clutched cranial perforators, used in craniotomy procedures, limits their performance under certain clinical conditions and can, in some cases, impose the risk of severe brain injury on patients undergoing the procedure. An additional safety mechanism could help in mitigating these risks. In this work, we examine the use of diffuse reflectance spectroscopy as a potential fallback mechanism for near real-time detection of the bone-brain boundary. Monte Carlo simulation of a two layer model with optical properties of bone and brain at 530 and 850 nm resulted in a detectable change in diffuse reflectance signal when approaching the boundary. The simulated results were used to guide the development of an experimental drill control system, which was tested on 10 sheep craniums and yielded 88.1 % success rate in the detection of the approaching bone-brain boundary.

Diffuse reflectance spectroscopy-enhanced drill for bone boundary detection.

Intramedullary nailing is a routine orthopedic procedure used for treating fractures of femoral or tibial shafts. A critical part of this procedure involves the drilling of pilot holes in both ends of the bone for the placement of the screws that will secure the IM rod to sections of the fractured bone. This step introduces a risk of soft tissue damage because the drill bit, if not stopped in time, can transverse the bone-tissue boundary into the overlying muscle, causing unnecessary injury and prolonging healing time due to periosteum damage. In this respect, detecting the bone-tissue boundary before break-through can reduce the risks and complications associated with intramedullary nailing. Hence, in the present study, a two-wavelength diffuse reflectance spectroscopy technique was integrated into a surgical drill to optically detect bone-tissue boundary and automatically trigger the drill to stop. Furthermore, Monte-Carlo simulations were used to estimate the maximum distance from within the bone at which the bone-tissue boundary could be detected using DRS. The simulation results estimated that the detection distance, termed the "look-ahead-distance" was ∼1.5 mm for 1.3 mm source-detector fiber separation. Experimental measurements with 1.3 mm source-detector fiber separation showed that the look-ahead-distance was in the order of 250 µm in experiments with set drill rate and in the range of 1 mm in experiments where the holes were drilled by hand. Despite this difference, the automated DRS enhanced drill successfully detected the approaching bone tissue boundary when tested on samples of bovine femur and muscle tissue.

Missed opportunities for type 2 diabetes mellitus screening among women with a history of gestational diabetes mellitus.

OBJECTIVES: We sought to determine rates and factors associated with screening for type 2 diabetes mellitus (DM) in women with a history of gestational diabetes mellitus. METHODS: We retrospectively studied women with diagnosed gestational diabetes mellitus who delivered at a university-affiliated hospital (n=570). Data sources included medical and administrative record review. Main outcome measures were the frequency of any type of glucose testing at least 6 weeks after delivery and the frequency of recommended glucose testing. We assessed demographic data, past medical history, and prenatal and postpartum care characteristics. RESULTS: Rates of glucose testing after delivery were low. Any type of glucose testing was performed at least once after 38% of deliveries, and recommended glucose testing was performed at least once after 23% of deliveries. Among women with at least 1 visit to the health care system after delivery (n=447), 42% received any type of glucose test at least once, and 35% received a recommended glucose test at least once. Factors associated with testing were being married, having a visit with an endocrinologist after delivery, and having more visits after delivery. CONCLUSIONS: These findings suggest that most women with gestational diabetes mellitus are not screened for type 2 DM after delivery. Opportunities for DM prevention and early treatment are being missed.

A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes.

OBJECTIVE: To compare the efficacy and safety of continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI) in older adults with insulin-treated type 2 diabetes and to assess treatment satisfaction and quality of life. RESEARCH DESIGN AND METHODS: Adults (n = 107) > or =60 years of age (mean age 66 years) with insulin-treated type 2 diabetes (mean duration 16 years, BMI 32 kg/m(2), and HbA(1C) [A1C] 8.2%) were randomized to CSII (using insulin lispro) or MDI (using insulin lispro and insulin glargine) in a two-center, 12-month, prospective, randomized, controlled clinical trial. Efficacy was assessed with A1C, safety by frequency of hypoglycemia, and treatment satisfaction and quality of life with the Diabetes Quality of Life Clinical Trial Questionnaire and the 36-item short-form health survey, version 2. RESULTS: Forty-eight CSII subjects (91%) and 50 MDI subjects (93%) completed the study. Mean A1C fell by 1.7 +/- 1.0% in the CSII group to 6.6% and by 1.6 +/- 1.2% in the MDI group to 6.4%. The difference in A1C between treatment groups was not statistically significant (P = 0.20). Eighty-one percent of CSII subjects and 90% of MDI subjects experienced at least one episode of minor (self-treated) hypoglycemia (P = 0.17), and three CSII and six MDI subjects experienced severe hypoglycemia (P = 0.49). Rates of severe hypoglycemia were similarly low in the two groups (CSII 0.08 and MDI 0.23 events per person-year, P = 0.61). Weight gain did not differ between groups (P = 0.70). Treatment satisfaction improved significantly with both CSII and MDI (P < 0.0001), and the difference between groups was not statistically significant (P = 0.58). CONCLUSIONS: In older subjects with insulin-treated type 2 diabetes, both CSII and MDI achieved excellent glycemic control with good safety and patient satisfaction.

Opportunistic screening for diabetes in routine clinical practice.

OBJECTIVE: Since 1997, the American Diabetes Association has recommended that nondiabetic individuals >/=45 years of age be screened for diabetes at least every 3 years. We sought to characterize the frequency, methods, and results of diabetes screening in routine clinical practice. RESEARCH DESIGN AND METHODS: We studied opportunistic screening in nondiabetic members of a health maintenance organization >/=45 years of age who were assigned to a large, integrated, academic health care delivery system. Screening was defined as the first glucose, HbA(1c), or oral glucose tolerance test (OGTT) performed between 1 January 1998 and 31 December 2000. Chart review was performed to determine the prevalence of diabetes risk factors and to describe follow-up. RESULTS: Of 8,286 nondiabetic patients >/=45 years of age, 69% (n = 5,752) were screened. The frequency of screening was greater in patients with one or more primary care visits and increased with age. Women were more likely to be screened than men, and patients with at least one diabetes risk factor were more likely to be screened than those without risk factors. Random plasma glucose was the most common screening test (95%). Four percent (n = 202) of those screened had abnormal results. Only 38% (n = 77) of those with abnormal results received appropriate follow-up, and 17% (n = 35) were diagnosed with diabetes within 6 months of screening. The yield of screening was very low (0.6%, 35 of 5,752). CONCLUSIONS: Despite frequent screening and appropriate targeting of high-risk patients, follow-up of patients with abnormal results is uncommon and the yield of screening is low. Interventions are needed to help physicians recognize and provide appropriate follow-up for patients with potentially abnormal random glucose levels.

Community-based screening for diabetes in Michigan.

OBJECTIVE: To describe and evaluate a community-based diabetes screening program supported by the Michigan Department of Community Health. RESEARCH DESIGN AND METHODS: Between 1 June 1999 and 31 December 1999, community screening for diabetes was conducted by voluntary organizations using a standard protocol, American Diabetes Association (ADA) questionnaires, and ADA capillary plasma glucose criteria. RESULTS: A total of 3506 individuals were screened, 14% of whom did not meet criteria for screening. Of the 3031 individuals appropriately screened, 57% were classified as being at high risk based on the ADA questionnaire and 5% had positive screening tests based on ADA capillary plasma glucose criteria. Despite systematic follow-up, the screening program's yield of individuals with undiagnosed diabetes was <1%. CONCLUSIONS: Community screening for diabetes conducted according to ADA recommendations was extremely inefficient at identifying individuals with undiagnosed diabetes. The ADA diabetes screening questionnaire resulted in many false positive tests, and the ADA criteria for positive plasma glucose tests likely missed a substantial portion of individuals with undiagnosed diabetes. Relying on biochemical tests such as random plasma glucose, changing the criteria for a positive plasma glucose test, targeting racial and ethnic minority groups, and targeting medically underserved individuals might improve the yield of community-based diabetes screening.

Improving diabetes processes of care in managed care.

OBJECTIVE: To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practices. RESEARCH DESIGN AND METHODS: Nine practices providing care to managed care patients were randomly assigned as intervention or comparison sites. Intervention-site subjects had Annual Diabetes Assessment Program (ADAP) assessments (HbA(1c), blood pressure, lipids, smoking, retinal photos, urine microalbumin, and foot examination) at years 1 and 2. Comparison-site subjects had ADAP assessments at year 2. At Intervention sites, year 1 ADAP results were reviewed with subjects, mailed to providers, and incorporated into electronic medical records with guideline-generated suggestions for treatment and follow-up. Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessments. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models. RESULTS: Of 284 eligible subjects, 103 of 173 (60%) at the Intervention sites and 71 of 111 (64%) at the comparison sites participated; 83 of 103 (81%) of the intervention-site subjects returned for follow-up at year 2. Performance of the six recommended assessments improved in intervention-site subjects at year 2 compared with year 1 (5.8 vs. 4.3, P = 0.0001) and compared with comparison-site subjects at year 2 (4.2, P = 0.014). No significant changes were noted in intermediate outcomes. CONCLUSIONS: The ADAP significantly improved processes of care but not intermediate outcomes. Additional interventions are needed to improve intermediate outcomes.

The direct medical cost of type 2 diabetes.

OBJECTIVE: To describe the direct medical costs associated with type 2 diabetes, as well as its treatments, complications, and comorbidities. RESEARCH DESIGN AND METHODS: We studied a random sample of 1,364 subjects with type 2 diabetes who were members of a Michigan health maintenance organization. Demographic characteristics, duration of diabetes, diabetes treatments, glycemic control, complications, and comorbidities were assessed by surveys and medical chart reviews. Annual resource utilization and costs were assessed using health insurance claims. The log-transformed annual direct medical costs were fitted by multiple linear regression to indicator variables for demographics, treatments, glycemic control, complications, and comorbidities. RESULTS: The median annual direct medical costs for subjects with diet-controlled type 2 diabetes, BMI 30 kg/m(2), and no microvascular, neuropathic, or cardiovascular complications were 1,700 dollars for white men and 2,100 dollars for white women. A 10-kg/m(2) increase in BMI, treatment with oral antidiabetic or antihypertensive agents, diabetic kidney disease, cerebrovascular disease, and peripheral vascular disease were each associated with 10-30% increases in cost. Insulin treatment, angina, and MI were each associated with 60-90% increases in cost. Dialysis was associated with an 11-fold increase in cost. CONCLUSIONS: Insulin treatment and diabetes complications have a substantial impact on the direct medical costs of type 2 diabetes. The estimates presented in this model may be used to analyze the cost-effectiveness of interventions for type 2 diabetes.