Table 1: Technologies for Noninvasive Diabetes Management⁷.

Technology Employed	Company	Device	Target Site	Characteristics
A) Main devices with substantiated claims:
Reverse iontophoresis	Animas Technologies (Cygnus Inc.)	GlucoWatch© G2 Biographer	Wrist skin	Advantages: CE and FDA approved; takes into account the skin temperature and perspiration fluctuations; alarm and trend indicators for rapid changes in glucose readings; event marking, data download, software analysis, and data-storage capacity Disadvantages: Expensive; requires 2-3 hour warm-up period, calibration using a standard blood glucose meter and replacement of disposable pad every 12 h; difficulty in calibration; inaccuracy due to subject’s movement, exercising, sweating or rapid temperature changes; cannot be used in water; skin irritation was the main drawback; it shuts down automatically in cases of sweating, works better at high glucose levels and does not reliably detect hypoglycemia
Bioimpedence spectroscopy	Biovotion AG (Solianis Monitoring AG; Pendragon)	GlucoTrack™	Wrist skin	Advantages: CE approved; data downloading via USB, data analysis, software, data-storage capacity and long-lasting battery; alerts for rapid changes in glucose concentration and hypoglycemia; self-correction for changes in impedance due to variations in temperature. Disadvantages: Glucose readings vary in individuals; requires additional calibration for differences in skin and underlying tissues among individuals; difficulty in calibration; Pendra tape needs to be changed every 24 h; device needs to be reattached at the same spot where it was calibrated followed by 1-hour equilibrium time; poor correlation of only 35 % with glucose meters; Clark Error Grid Analysis indicated 4.3 % readings in error zone E; patient must rest for 60 min for equilibration before the reading; it cannot be used in many subjects whose skin types and basic skin impedances are unsuitable for the device; poor accuracy in post-marketing validation study
Ultrasound, electromagnetic and heat capacity	integrity Applications Ltd	GlucoTrack™	Ear lobe skin	Advantages: High precision and accuracy as it employs various Ni-CGM techniques; easy calibration procedure; calibration is valid for one month; USB and IR connectivity, alerts for hypo- and hyperglycemia, multi-user support, data-storage capacity, and software for data analysis; readings were unaffected by daily routine activities; high accuracy in clinical trials; good correlation with glucose meters and glucose analyzers; compact and lightweight device with large LCD screen Disadvantages: Requires individual calibration against invasive basal and post-prandial blood glucose references before it can be used for glucose measurements; needs improvements in calibration procedure and algorithm for data processing
Occlusion NIR spectroscopy	OrSense Ltd	OrSense NBM-200G	Fingertip skin	Advantages: CE approved; allows noninvasive measurement of glucose as well as hemoglobin and oxygen saturation; portable, easy-to-use and measures glucose in less than a minute; data-storage capacity, alarm alerts, trend data analysis and integrated wireless telemetry; does not require frequent calibrations; easy calibration procedure; measures glucose continuously for 24 h; good accuracy in clinical trials that was similar to glucose meters Disadvantages: Not mentioned
Laser microporation	SpectRx Inc. (Guided Therapeutics, Inc.)		Skin	Advantages: Glucose measurements in the interstitial fluid by this device correlated well with those by commercial analyzer and glucose meters; easy calibration procedure; wireless telemetry Disadvantages: Requires calibration with a blood glucose meter; glucose measurements in interstitial fluid have time lag of 2-4 min with respect to blood
Prelude® SkinPrep System	Echo Therapeutics, Inc. (Sontra Medical Corporation)	Symphony™	Skin	Advantages: Brief warm-up period; glucose measurement every minute; wireless telemetry; alarm alerts for rapid changes in glucose concentration; no skin irritation; highly successful clinical trials; good correlation with glucose analyzers and glucose meters Disadvantages: Not mentioned
B) Systems lacking well-documented clinical trials:
NIR spectroscopy	Biocontrol Technology, Inc.	Diasensor©	Forearm skin	Large size and could not detect hypoglycemic events
Photoacoustic spectroscopy	Glucon Medical Ltd	Aprise©	Forearm skin	Compact, lightweight, and measures glucose every 3 seconds inside the blood vessels with high specificity and sensitivity
Impedence spectroscopy	Calisto Medical, Inc.	Glucoband©	Wrist skin	Data transfer via USB; data-storage capacity; long-lasting batteries; rapid self-calibration before each measurement; alerts for hypo- and hyperglycemia; no disposable waste
NIR spectroscopy	LifeTrac Systems Inc.	SugarTrac™	Skin	Blood-glucose measurement in less than a minute; safe for patient as device components do not touch the skin
NIR spectroscopy	Futrex medical instrumentation, Inc.	Dream Beam	Fingertip skin	Portable, compact, and battery-powered but requires individual calibration
Reverse iontophoresis	KMH Co. Ltd	GluCall	Skin	Korean FDA approved; alarm alerts for hypo- and hyperglycemia; data-storage capacity; PC connectivity and software-based analysis; but requires warm-up period of 1 hour before measurement and calibration with blood glucose meter after measurement
Elecromagnetic sensing	ArithMed GmbH and Samsung Fine Chemicals Co. Ltd	GluControl GC300®	Fingertip skin	Portable, battery-powered, and data-storage capacity
Thermal spectroscopy	Hitachi Ltd		Fingertip skin	Compact device with integrated sensors to detect physiologic parameters
Novel fluid extraction technology	University of Missouri-St Louis		Skin	Compact device with novel fluid-extraction technology to provide stable interstitial fluid samples
Electromagnetic sensing	University of Missouri-St Louis	TouchTrak Pro 200	Fingertip skin	Portable device with high cost
Optical coherence tomography	University of Missouri-St Louis		Skin	Portable
Fluorescence technology	University of Missouri-St Louis		intra-vascular	Employs GluGlow technology based on a glucose-sensing polymer that glows in the presence of glucose
Thermal emission spectroscopy	University of Missouri-St Louis		Tympanic membrane	Portable handheld device that determines blood glucose level in 10 seconds
Raman spectroscopy	University of Missouri-St Louis		Fingertip skin	Portable; employs proprietary tissue modulation process for blood-glucose measurements.
NIR spectroscopy	University of Missouri-St Louis		Skin	Portable; employs proprietary ReSense technology based on the reflection of NIR light from the skin surface
Raman spectroscopy	University of Missouri-St Louis		Skin	Compact, wearable, and water-resistant; glucose measurement in 3 minutes; accuracy similar to currently available continuous glucose monitoring systems; less-expensive glucose determination than glucose meters based on three finger-stick tests per day over 4 years. Clinical studies and trials are needed to validate the results; CE Mark regulatory approval is still pending
Raman spectroscopy	University of Missouri-St Louis		Finger or arm skin	Portable; measures interstitial fluid glucose; use an algorithm to determine the blood glucose level from the glucose concentration in interstitial fluid; uses a DCC-based calibration procedure for precise blood glucose measurements. Clinical studies are required to validate the system; tremendous efforts are still needed to develop a miniaturized device prototype
NIR spectroscopy	University of Missouri-St Louis			Portable device prototype that detects blood glucose in the capillaries of finger with high precision in just 1 second. Clinical testing and regulatory approvals are required

DCC = dynamic concentration correction; FDA = US Food and Drug Administration; NI-CGM = noninvasive continuous glucose monitoring; NIR = near-infrared.