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From 2001 to 2023, 17 (14%) of 120 neonates with confirmed herpes simplex virus infection tested positive for herpes simplex virus by polymerase chain reaction (PCR) from only mucosal sites without a clinical mucosal lesion. Whether mucosal PCR positivity reflects early infection that may lead to recognizable disease, transient colonization, or a false-positive PCR result remains a clinical conundrum and warrants further study., Competing Interests: Declaration of Competing Interest A.M. has received fees for participation in Advisory Boards from Janssen, Merck, Pfizer, AstraZeneca and Sanofi-Pasteur as well as research grants from NIH, Merck, and Janssen. None contributed to study design, collection, analysis, and interpretation of data, writing of the report, and decision to submit the manuscript for publication. Other authors have no conflict of interest relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Winter field survival (WFS) in autumn-seeded winter cereals is a complex trait associated with low temperature tolerance (LTT), prostrate growth habit (PGH), and final leaf number (FLN). WFS and the three sub-traits were analyzed by a genome-wide association study of 96 rye (Secale cereal L.) genotypes of different origins and winter-hardiness levels. A total of 10,244 single nucleotide polymorphism (SNP) markers were identified by genotyping by sequencing and 259 marker-trait-associations (MTAs; p < 0.01) were revealed by association mapping. The ten most significant SNPs (p < 1.49e-04) associated with WFS corresponded to nine strong candidate genes: Inducer of CBF Expression 1 (ICE1), Cold-regulated 413-Plasma Membrane Protein 1 (COR413-PM1), Ice Recrystallization Inhibition Protein 1 (IRIP1), Jasmonate-resistant 1 (JAR1), BIPP2C1-like protein phosphatase, Chloroplast Unusual Positioning Protein-1 (CHUP1), FRIGIDA-like 4 (FRL4-like) protein, Chalcone Synthase 2 (CHS2), and Phenylalanine Ammonia-lyase 8 (PAL8). Seven of the candidate genes were also significant for one or several of the sub-traits supporting the hypothesis that WFS, LTT, FLN, and PGH are genetically interlinked. The winter-hardy rye genotypes generally carried additional allele variants for the strong candidate genes, which suggested allele diversity was a major contributor to cold acclimation efficiency and consistent high WFS under varying field conditions., (© 2022. The Author(s).)

Background: Pre-harvest sprouting (PHS) is a major problem for wheat production due to its direct detrimental effects on wheat yield, end-use quality and seed viability. Annually, PHS is estimated to cause > 1.0 billion USD in losses worldwide. Therefore, identifying PHS resistance quantitative trait loci (QTLs) is crucial to aid molecular breeding efforts to minimize losses. Thus, a doubled haploid mapping population derived from a cross between white-grained PHS susceptible cv AAC Innova and red-grained resistant cv AAC Tenacious was screened for PHS resistance in four environments and utilized for QTL mapping., Results: Twenty-one PHS resistance QTLs, including seven major loci (on chromosomes 1A, 2B, 3A, 3B, 3D, and 7D), each explaining ≥10% phenotypic variation for PHS resistance, were identified. In every environment, at least one major QTL was identified. PHS resistance at most of these loci was contributed by AAC Tenacious except at two loci on chromosomes 3D and 7D where it was contributed by AAC Innova. Thirteen of the total twenty-one identified loci were located to chromosome positions where at least one QTL have been previously identified in other wheat genotype(s). The remaining eight QTLs are new which have been identified for the first time in this study. Pedigree analysis traced several known donors of PHS resistance in AAC Tenacious genealogy. Comparative analyses of the genetic intervals of identified QTLs with that of already identified and cloned PHS resistance gene intervals using IWGSC RefSeq v2.0 identified MFT-A1b (in QTL interval QPhs.lrdc-3A.1) and AGO802A (in QTL interval QPhs.lrdc-3A.2) on chromosome 3A, MFT-3B-1 (in QTL interval QPhs.lrdc-3B.1) on chromosome 3B, and AGO802D, HUB1, TaVp1-D1 (in QTL interval QPhs.lrdc-3D.1) and TaMyb10-D1 (in QTL interval QPhs.lrdc-3D.2) on chromosome 3D. These candidate genes are involved in embryo- and seed coat-imposed dormancy as well as in epigenetic control of dormancy., Conclusions: Our results revealed the complex PHS resistance genetics of AAC Tenacious and AAC Innova. AAC Tenacious possesses a great reservoir of important PHS resistance QTLs/genes supposed to be derived from different resources. The tracing of pedigrees of AAC Tenacious and other sources complements the validation of QTL analysis results. Finally, comparing our results with previous PHS studies in wheat, we have confirmed the position of several major PHS resistance QTLs and candidate genes., (© 2021. Her Majesty the Queen in Right of Canada, as represented by the Minister of Agriculture and Agri-Food Canada.)

Overwintering cereals accumulate low temperature tolerance (LTT) during cold acclimation in the autumn. Simultaneously, the plants adjust to the colder season by making developmental changes at the shoot apical meristem. These processes lead to higher winter hardiness in winter rye varieties ( Secale cereale L.) adapted to Northern latitudes as compared to other cereal crops. To dissect the winter-hardiness trait in rye, a panel of 96 genotypes of different origins and growth habits was assessed for winter field survival (WFS), LTT, and six developmental traits. Best Linear Unbiased Estimates for WFS determined from five field trials correlated strongly with LTT (r = 0.90, p < 0.001); thus, cold acclimation efficiency was the major contributor to WFS. WFS also correlated strongly ( p < 0.001) with final leaf number (r = 0.80), prostrate growth habit (r = 0.61), plant height (r = 0.34), but showed weaker associations with top internode length (r = 0.30, p < 0.01) and days to anthesis (r = 0.25, p < 0.05). The heritability estimates ( h 2 ) for WFS-associated traits ranged from 0.45 (prostrate growth habit) to 0.81 (final leaf number) and were overall higher than for WFS ( h 2 = 0.48). All developmental traits associated with WFS and LTT are postulated to be regulated by phytohormone levels at shoot apical meristem.

Early seeding has been suggested as a method of increasing the grain yield and grain yield stability of wheat ( Triticum aestivum L .) in the Northern Great Plains. The point at which early seeding results in a decrease in grain yield has not been clearly identified. Changes in climatic conditions have increased frost-free periods and increased temperatures during grain filling, which can either be taken advantage of or avoided by seeding earlier. Field trials were conducted in western Canada from 2015 to 2018 to evaluate an ultra-early wheat planting system based on soil temperature triggers as opposed to calendar dates. Planting began when soil temperatures at 5 cm depth reached 0°C and continued at 2°C intervals until 10°C, regardless of calendar date. Conventional commercial spring wheat genetics and newly identified cold tolerant spring wheat lines were evaluated to determine if ultra-early wheat seeding systems required further development of specialized varieties to maintain system stability. Ultra-early seeding resulted in no detrimental effect on grain yield. Grain yield increased at sites south of 51° latitude N, and was unaffected by ultra-early seeding at sites north of 51° latitude N. Grain protein content, kernel weight, and bulk density were not affected by ultra-early seeding. Optimal seeding time was identified between 2 and 6°C soil temperatures. A greater reduction in grain yield was observed from delaying planting until soils reached 10°C than from seeding into 0°C soils; this was despite extreme environmental conditions after initial seeding, including air temperatures as low as -10.2°C, and as many as 37 nights with air temperatures below 0°C. Wheat emergence ranged from 55 to 70%, and heads m -2 decreased with delayed seeding while heads plant -1 did not change. Cold tolerant wheat lines did not increase stability of the ultra-early wheat seeding system relative to the conventional spring wheat check, and are therefore not required for growers to adopt ultra-early seeding. The results of this study indicate that growers in western Canada can successfully begin seeding wheat earlier, with few changes to their current management practices, and endure less risk than delaying seeding until soil temperatures reach 10°C or greater., (Copyright © 2020 Collier, Spaner, Graf and Beres.)

Breeding for solid-stemmed durum (Triticum turgidum L. var durum) and common wheat (Triticum aestivum L.) cultivars is one strategy to minimize yield losses caused by the wheat stem sawfly (Cephus cinctus Norton). Major stem-solidness QTL have been localized to the long arm of chromosome 3B in both wheat species, but it is unclear if these QTL span a common genetic interval. In this study, we have improved the resolution of the QTL on chromosome 3B in a durum (Kofa/W9262-260D3) and common wheat (Lillian/Vesper) mapping population. Coincident QTL (LOD = 94-127, R2 = 78-92%) were localized near the telomere of chromosome 3BL in both mapping populations, which we designate SSt1. We further examined the SSt1 interval by using available consensus maps for durum and common wheat and compared genetic to physical intervals by anchoring markers to the current version of the wild emmer wheat (WEW) reference sequence. These results suggest that the SSt1 interval spans a physical distance of 1.6 Mb in WEW (positions 833.4-835.0 Mb). In addition, minor QTL were identified on chromosomes 2A, 2D, 4A, and 5A that were found to synergistically enhance expression of SSt1 to increase stem-solidness. These results suggest that developing new wheat cultivars with improved stem-solidness is possible by combining SSt1 with favorable alleles at minor loci within both wheat species.

Development of transgenic triticale as a platform for novel bio-industrial products is predicated on an environmental biosafety assessment that quantifies the potential risks associated with its release. Pollen-mediated gene flow to related species and conventional triticale varieties is one pathway for transgene movement. A tier 1 quantification of triticale hybridization was conducted by emasculating and hand pollinating flowers under greenhouse conditions. Approximately 2000 manual pollinations were conducted for each cross and its reciprocal between two triticale genotypes: a modern triticale cultivar (AC Alta) and primary triticale (89TT108), and common wheat, durum wheat and rye. The frequency of outcrossing, hybrid seed appearance and weight, and F(1) emergence and fertility were recorded. Outcrossing, F(1) emergence and fertility rates were high from crosses between triticale genotypes. Outcrossing in inter-specific crosses was influenced by the species, and the genotype and gender of the triticale parent. In crosses to common and durum wheat where triticale was the male parent, outcrossing was > or =73.0% and > or =69.5%, respectively, but < or =23.9% and < or =3.0% when triticale was the female parent. Overall, outcrossing with rye was lower than with common and durum wheat. F(1) hybrid emergence was greater when triticale was the female parent. With the exception of a single seed, all wheat-triticale F(1) hybrid seeds were non-viable when triticale was the male parent in the cross. Only seven durum wheat-triticale F(1) hybrids emerged from 163 seeds sown, and all were produced with triticale 89TT108 as female parent. With rye, 8 F(1) hybrids emerged from 38 seeds sown, and all were produced from crosses to AC Alta; five with AC Alta as the female parent and three as the male. Interspecific F(1) hybrids were self-sterile, with the exception of those produced in crosses between common wheat and triticale where triticale was the female parent. Tier 2 hybridization quantification will be conducted under field conditions.

High yield potential and the wide adaptability of wheat-rye T1BL·1RS translocation lines are attractive to breeders. The wheat-rye lines Lankao 1, 3, 4, and 5 were resistant to a wide spectrum of wheat powdery mildew (Blumeria graminis f. sp. tritici) isolates from both China and Canada. They also were resistant to a mixture of wheat stem rust (Puccinia graminis f. sp. tritici) pathotypes (98WSR) and wheat stripe rust (P. striiformis f. sp. tritici) races from western Canada and China. Colonization of wheat curl mite (WCM) (Aceria tosichella) resulted in slower development of rolling and trapping leaves in the Lankao lines than in the WCM-susceptible check cultivars. The delayed development of Wheat streak mosaic (WSM) symptoms on Lankao lines was observed when transmitted by viruliferous WCM, even though they were susceptible to Wheat streak mosaic virus (WSMV). This effect of Lankao lines on limiting the spread of WSM was comparable with other known sources of WCM resistance. Sequential C-banding and genomic in situ hybridization analyses revealed the presence of a pair of T1BL·1RS translocated chromosomes in the Lankao lines. Segregation analysis of the F 2 progeny plants derived from crosses between Lankao 4 and the susceptible wheat cvs. Mingxian 169 and Lovrin 13 indicated that a single dominant gene was responsible for the isolate-specific resistance against wheat powdery mildew in Lankao 4. Polymerase chain reaction analysis using an STS marker amplified rye chromatin in powdery mildew-resistant and -susceptible F 2 plants of the Mingxian 169 × Lankao 4 cross demonstrated that the resistance of Lankao 4 was not controlled by a gene or genes located on the rye chromosome arm of T1BL·1RS. The resistance of the Lankao lines to diseases and limitation of the spread of WSMV, in combination with good quality and high yield potential, makes them useful for wheat improvement and production.

Common root rot, caused by Cochliobolus sativus (Ito and Kurib) Drechs. ex Dastur, is a major soil-borne disease of spring and winter wheat (Triticum aestivum L. em Thell.) on the Canadian prairies. Resistance to common root rot from Thinopyrum ponticum (Podp.) Liu and Wang was transferred into wheat via crossing with Agrotana, a resistant wheat - Th. ponticum partial amphiploid line. Evaluation of common root rot reactions showed that selected advanced lines with blue kernel color derived from a wheat x Agrotana cross expressed more resistance than the susceptible T. aestivum 'Chinese Spring' parent and other susceptible wheat check cultivars. Cytological examination revealed 41 to 44 chromosomes in the advanced lines. Genomic in situ hybridization, using total genomic DNA from Pseudoroegneria strigosa (M. Bieb) A. Löve (St genome) as a probe, demonstrated that the blue kernel plants had two pairs of spontaneously translocated J-Js and Js-J chromosomes derived from the J and Js genome of Th. ponticum. The presence of these translocated chromosomes was associated with increased resistance of wheat to common root rot. The lines with blue aleurone color always had a subcentromeric Js-J translocated chromosome. The subtelocentric J-Js translocated chromosome was not responsible for the blue kernel color. The genomic in situ hybridization analysis on meiosis revealed that the two spontaneous translocations were not reciprocal translocations.

Leaf rust (caused by Puccinia triticina Eriks.) occurs annually in most wheat-growing areas of the world. Thinopyrum ponticum (Podp.) Z.-W. Liu & R.-C. Wang has provided several leaf rust resistance genes to protect wheat from this fungal disease. Three chromosome substitution lines, Ji806, Ji807, and Ji859, and two chromosome addition lines, Ji791 and Ji924, with a winter growing habit were developed from crosses between wheat (Triticum aestivum L. em Thell.) and the wheat - Th. ponticum partial amphiploid line 693. These lines were resistant to leaf rust isolates from China. Sequence-tagged site (STS) analysis with the J09-STS marker, which is linked to the gene Lr24, revealed that the partial amphiploid line 693 and all of the substitution and addition lines carried gene Lr24. Genomic in situ hybridization (GISH) analysis was carried out on chromosome preparations using total genomic DNA from Pseudoroegneria strigosa (M. Bieb) A. Löve (St genome, 2n = 14) as a probe in the presence of total genomic DNA from T. aestivum 'Chinese Spring' wheat (ABD genomes, 2n = 42). The GISH analysis demonstrated that these lines had a pair of chromosomes displaying the typical pattern of a Js genome chromosome. This indicates that the chromosome that carries gene Lr24 belonged to the Js genome of Th. ponticum. In addition to 40 wheat chromosomes, eight Js and eight J genome chromosomes were also differentiated by GISH in the partial amphiploid line 693. Since most sources of Lr24 have a red grain color, the white-colored seeds in all of these substitution and addition lines, together with high protein content in some of the lines, make them very useful as a donor source for winter wheat breeding programs.

Thinopyrum intermedium (2n = 6x = 42, JJJsJsSS) is potentially a useful source of resistance to wheat streak mosaic virus (WSMV) and its vector, the wheat curl mite (WCM). Five partial amphiploids, namely Zhong 1, Zhong 2, Zhong 3, Zhong 4, and Zhong 5, derived from Triticum aestivum x Thinopyrum intermedium crosses produced in China, were screened for WSMV and WCM resistance. Zhong 1 and Zhong 2 had high levels of resistance to WSMV and WCM. The other three partial amphiploids, Zhong 3, 4, and 5, were resistant to WSMV, but were susceptible to WCM. Genomic in situ hybridization (GISH) using a genomic DNA probe from Pseudoroegneria strigosa (SS, 2n = 14) demonstrated that two partial amphiploids, Zhong 1 and Zhong 2, have almost the identical 10 Th. intermedium chromosomes, including four Js, four J, and two S genome chromosomes. Both of them carry two pairs of J and a pair of Js genome chromosomes and two different translocations that were not observed in the other three Zhong lines. The partial amphiploids Zhong 3, 4, and 5 have another type of basic genomic composition, which is similar to a reconstituted alien genome consisting of four S and four Js genome chromosomes of Th. intermedium (Zhong 5 has two Js chromosomes plus two Js-W translocations) with six translocated chromosomes between S and Js or J genomes. All three lines carry a specific S-S-Js translocated chromosome, which might confer resistance to barley yellow dwarf virus (BYDV-PAV). The present study identified a specific Js2 chromosome present in all five of the Zhong lines, confirming that a Js chromosome carries WSMV resistance. Resistance to WCM may be linked with J or Js chromosomes. The discovery of high levels of resistance to both WSMV and WCM in Zhong 1 and Zhong 2 offers a useful source of resistance to both the virus and its vector for wheat breeding programs.

Wheat curl mite (WCM), Aceria tosichella, is the vector of Wheat streak mosaic virus (WSMV), a destructive viral pathogen in wheat (Triticum aestivum). Genetic resistance to WCM colonization can reduce the incidence of wheat streak mosaic. Chromosome 6V in Hay-naldia villosa is a new source of WCM resistance. We compared variation in resistance among different sources of H. villosa chromosome 6V and 6VS lines to WCM and WSMV and their effectiveness in controlling the incidence of WSMV following exposure to viruliferous WCM. WCM resistance varied among the 6V and 6VS lines depending on the H. villosa parent. The 6V substitution lines Yi80928, GN21, and GN22 derived from an accession of H. villosa from China, and the 6VS translocation lines 92R137, 92R178, and Sub6V from an H. villosa accession collected from the United Kingdom were uniformly resistant to WCM colonization. In contrast, the 6V substitution line RW15 and a 6VS translocation line Pm33 developed from an H. villosa collection from the former Union of Soviet Socialist Republics were susceptible to WCM. All 6V and 6VS lines were susceptible to WSMV when manually inoculated. However, symptom expression was delayed in the WCM-resistant 6V and 6VS lines after exposure to viruliferous WCM. The 6V and 6VS lines differed in their ability to control WSMV infection. WCM-susceptible lines RW15 and Pm33 had no effect on controlling the infection by WSMV. Lines GN21 and GN22 were the most effective of the three H. villosa sources in limiting the spread of WSMV. Their high yield potential and protein content, in combination with resistance to stripe rust (Puccinia striiformis f. sp. tritici) and powdery mildew (Erysiphe graminis f. sp. tritici), make GN21 and GN22 promising sources of WCM resistance.

Background: The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes., Methods: Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean)., Results: Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events., Conclusions: These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

The influence of therapy of hyperglycemia on the progression of diabetic neuropathy is unclear. We studied variables of glycemia and motor and sensory nerve conduction velocity in a group of 18 non-insulin-dependent diabetic subjects before and after institution of diabetes therapy. Diabetes therapy significantly reduced variables of glycemia after 1, 3, 6, and 12 months. Conduction velocity of the median motor nerve was improved from baseline at each time tested during treatment. In addition, peroneal and tibial motor nerve conduction velocities improved in patients whose levels of hyperglycemia were lowered. Moreover, extent of improvement of conduction velocity of some motor nerves was related to the degree of reduction of hyperglycemia. Sensory nerve conduction velocity was not altered by diabetes therapy. These findings support the hypothesis of a metabolic component to diabetic neuropathy and suggest that optimal glycemic control may be beneficial to patients with this disorder.

Concentrations of glycosylated hemoglobin (GHb) are elevated in diabetes mellitus and are believed to reflect previous metabolic control. To better define possible determinants of GHb in man, we investigated the relationship between GHb and both fasting plasma glucose (FPG) and basal insulin (IRI) in 42 normal subjects and 29 patients with maturity-onset diabetes. Concentrations of GHb in diabetic subjects (12.7 +/- 3.4, x +/- S.D., per cent total hemoglobin) were significantly higher than in normal subjects (8.2 +/- 1.2, p less than 0.001). In normal subjects, FPG (r = 0.52) and GHb (r = 0.58) (both p less than 0.001) correlated with age. GHb did not correlate with IRI in either group. However, GHb was closely associated with FPG in both normal (r = 0.60, p less than 0.001) and diabetic (r = 0.85, p less than 0.001) subjects. Linear regression analysis of the data for the two groups combined was highly significant (r = 0.91, p less than 0.001). However, the slope of the regression line for GHb versus FPG seen in normal subjects was significantly steeper than that of diabetic patients (p less than 0.005). A curve describing a nonenzymatic saturable model was also found to fit the data of the two groups combined (r = 0.85, p less than 0.001), suggesting the possible existence of a saturable system for glycosylation in man.

The objective of this study was to determine the relationship between nerve conduction velocity (NCV) and hyperglycemia and to assess the extent of NCV changes in adult-onset diabetic patients before and after diabetic treatment. Twenty-five diabetic males (mean age = 50.9 years) were tested twice prior to beginning diabetic treatment. Eighteen of these 25 were also tested at 1, 3, 6, and 12 months after initiation of therapy. Both groups were compared to 23 age-matched controls. Each test session consisted of NCV and clinical sensory and blood chemistry testing. The findings revealed that, before treatment average NCVs of the median, peroneal sural, and tibial nerves and H-reflex latency results were all significantly impaired in diabetic subjects (p less than 0.025). No difference was found between right and left NCVs of the same nerve (p less than 0.05) and NCVs in the lower as well as the upper extremities were significantly reduced (p less than 0.05). Thus, it appears that the neuropathy in these patients was symmetrical and diffuse. Peroneal and median motor nerves showed the greatest amount of NCV slowing when compared to normal values. Furthermore, median, peroneal, and tibial motor NCVs and H-reflex latencies correlated significantly with the degree of hyperglycemia in diabetic subjects before treatment. After initiation of diabetic treatment, median motor NCVs after 1, 3, 6 and 12 months showed significantly improvement when compared to baseline NCV values (all p less than 0.05). Also, the improvement in median NCVs after 3 and 13 months and peroneal NCV after 3 months directly correlated to decreased fasting plasma glucose levels (p less than 0.05).

The relationship between the pre-stimulus glucose level and immunoreactive insulin responses to a glucose challenge (20-g IV) was studied in normal subjects. When the steady-state pre-stimulus glucose concentration was lowered by a 0.33 mU.kg-1.min-1 insulin infusion or raised by a 900 mg/min glucose infusion, no effect on first phase insulin secretion (mean delta 3-5 min insulin level) was observed. In contrast, the second phase response (10-60 min insulin area after glucose pulse) to intravenous glucose fell during insulin infusion and increased during the glucose infusion. Overall, a linear relationship was found between the change of pre-stimulus glucose or level from the control to that during the insulin or glucose infusion and the change in second phase response (r = 0.65, n = 14, p less than 0.02). The effect of tolbutamide infusion (7 mg.m-2.min-1) when compared with saline control was to increase both first phase (+54 +/- 13 mU/l, n = 8, p less than 0.001, mean +/- SEM) and second phase (+972 +/- 256 mU. min-1.l-1, p less than 0.01) insulin secretion. It is concluded that the first phase response to a glucose pulse is independent of the steady-state pre-stimulus glucose concentration and is directly enhanced by tolbutamide; in contrast, second phase is related to both the steady-state pre-stimulus glucose level and tolbutamide. These findings suggest that changes in basal or pre-stimulus plasma glucose during therapy with sulphonylurea drugs may be expected to influence the second phase insulin responses to glucose challenge.

Diabetic neuropathy is defined, and theories of its pathogenesis are reviewed. Recent studies designed to investigate the influence of plasma glucose on nerve function in noninsulin-dependent diabetic patients are summarized. Motor nerve conduction velocities in the median and peroneal nerves were measured using a double-stimulus technique, and sensory conduction velocity was measured by conventional methods before and after therapy with oral agents or insulin. The degree of hyperglycemia was assessed by measurement of fasting plasma glucose and glycosylated hemoglobin concentrations. The degree of slowing in motor nerve conduction velocity in untreated patients was found to correlate with the fasting plasma glucose and glycosylated hemoglobin concentrations, but sensory nerve function, although abnormal, did not show such correlation. Reduction of hyperglycemia was associated with improvement in motor nerve conduction velocity in the peroneal and median motor nerves of these patients, but sensory nerve conduction velocity showed no such improvement. Improvement in median motor nerve conduction velocity was directly related to the degree of reduction in fasting plasma glucose concentration. These findings suggest that metabolic factors related to hyperglycemia are important in the impaired motor nerve function seen in noninsulin-dependent patients with maturity-onset diabetes.

The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the influence of hyperglycemia on nerve conduction, we studied 20 untreated maturity-onset diabetic patients and 23 normal control subjects of similar age. Nerve conduction velocity of motor (median, peroneal, and tibial) and sensory (median and sural) nerves in diabetic patients was significantly slowed and H-reflex latency time prolonged. Levels of fasting plasma glucose in diabetic subjects were correlated with slowed motor conduction velocity of the median, peroneal, and tibial nerves but not with sensory nerve conduction velocities. Levels of glycosylated hemoglobin, an index of long-term glycemia, were correlated with slowing of peroneal motor conduction velocity in diabetic patients. These associations could not be explained by patient age or duration of diabetes. These findings suggest that the degree of hyperglycemia of untreated maturity-onset diabetes contributes to the motor nerve conduction abnormalities in this disease.

Because levels of glycosylated hemoglobin (GHb) are increased in diabetes and reflect the previous metabolic control, clinicians and clinical investigators are finding increasing applications for measurements of GHb in diabetic patients. We report the characterization of a colorimetric assay procedure for GHb and compare its performance with that of a commonly used assay by ion-exchange chromatography. Although results of GHb determination by both methods correlate highly (r = 0.946, P less than 0.001), the two procedures estimate different glycosylated fractions. The colorimetric procedure is nonstoichiometric, requiring careful standardization of assay conditions, including the concentration of total hemoglobin in the assayed aliquot, to achieve precision and permit comparison of results. We characterized the effect of storage of hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetric method, but not by column chromatography, are reproducible on hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetric method, but not by column chromatography, are reproducible on hemolysates or packed erythrocytes stored frozen for at least 5 mo. A unique advantage of the colorimetric procedure is the capability to estimate GHb levels when variant hemoglobins, including fetal and sickle hemoglobins, are present.