Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes.

AIMS: Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes. METHODS: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). RESULTS: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. CONCLUSIONS: Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19-22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6-8 March 2019.

Isokinetic strength training of the hemiparetic knee: effects on function and spasticity.

PURPOSE: To determine whether isokinetic training can improve the strength of the hemiparetic knee musculature, functional mobility, and physical activity and to evaluate its effect on spasticity in long-term stroke survivors. DESIGN: Nonrandomized self-controlled trial. SUBJECTS: A volunteer sample of 15 community-dwelling stroke survivors of at least 6 months. INTERVENTION: A 6-week (3 days/week, 40 minutes/day) program consisting of warm-up, stretches, reciprocal knee extension and flexion isokinetic strengthening, and cool-down for the paretic limb. MAIN OUTCOME MEASURES: Peak isokinetic hamstring and quadriceps torque, quadriceps spasticity, gait velocity, timed Up and Go, timed stair climb, and the Human Activity Profile (HAP) scores were recorded at baseline, after training, and 4 weeks after training cessation (follow-up). RESULTS: Paretic muscle strength improved after training (p < .05) while tone remained consistent (p > .87). Gait velocity increased after training (p < .05) and at follow-up (p < .05). Changes in stair climbing and timed Up and Go were not significant (p > .37; p > .91), although subjects perceived gains in their physical abilities at follow-up (p < .01). CONCLUSIONS: Gains in strength and gait velocity without concomitant increases in muscle tone are possible after a short-term strengthening program for stroke survivors. The psychological benefit associated with physical activity is significant.

Lauryl sulphate haemoglobin: a non-hazardous substitute for HiCN in haemoglobinometry.

The haemiglobincyanide (HiCN) method for measuring haemoglobin is used extensively worldwide; its advantage is the ready availability of a stable and internationally accepted reference standard/calibrator. However, its use may create a problem, especially in automated analysers, as the waste disposal of large volumes of reagent containing cyanide may constitute a potential toxic hazard. As an alternative, conversion of haemoglobin to a sulphate derivative by nontoxic sodium lauryl sulphate has been proposed and is available as a commercial product from Toa Medical Electronics Co. Ltd., Japan. This evaluation has shown it to be as reliable and reproducible as HiCN for measuring haemoglobin at all concentrations, by both spectrophotometry and automated analyser. Maximum absorbance is at 534 nm. Total conversion occurs almost instantaneously, and includes methaemoglobin but not sulphaemoglobin. HbF is also measured. The only disadvantage is that solutions of haemoglobin-sulphate are stable for only a few hours at room temperature and up to three weeks at 4 degrees C. Thus, for standardization and calibration of instruments it is necessary to use a sample of blood or lysate the haemoglobin value of which has been assigned initially by the HiCN method.