Transverse growth of the mandibular body in untreated children: a longitudinal CBCT study.

OBJECTIVES: Currently available reports on mandibular transverse growth are limited to two-dimensional images and cross-sectional studies. The objective of this study was to examine transverse growth of the mandibular body in untreated growing individuals during the mixed dentition stage using longitudinal three-dimensional imaging. METHODS: CBCT images of 25 (13 females and 12 males) untreated subjects at two time points were analyzed. The average age was 9.1 years at T1 and 11.3 years at T2. Mandibular segmentation and superimposition were performed to obtain linear and angular measurements at different axial levels. RESULTS: At the superior (mental foramen) axial level, transverse growth between the buccal surfaces gradually increased from the premolars to the ramus. At the inferior axial level, significant transverse growth differences were detected between the ramus and the dentition regions. In contrast, between the lingual surfaces, both superior and inferior levels showed minimal change in the region under the dentition and a significant amount of resorption in the ramus region. This difference between buccal and lingual surface changes led to a mandibular body angulation change in the premolar and molar regions. In contrast, the overall mandibular body angulation measured from the posterior-most border of the mandible to the symphysis remained the same. Differences were detected between males and females, with males tending to exhibit greater transverse growth in the ramus region at the inferior level. CONCLUSIONS: The mandibular body exhibited different transverse growth patterns at different axial levels. Differences were also found between genders. CLINICAL RELEVANCE: An in-depth understanding of craniofacial growth and development is crucial to diagnosis and treatment planning. The current study provides additional insight into the transverse growth of the mandible.

Mandibular transverse dentoalveolar and skeletal changes associated with lip bumper and rapid maxillary expander: A cone-beam computed tomography study.

INTRODUCTION: Currently, there is little consensus regarding the spontaneous uprighting of the mandibular dentoalveolar complex in response to maxillary expansion, which poses the question about the necessity of combining mandibular treatment with rapid maxillary expansion to coordinate the maxilla and mandible transversely. This study aimed to evaluate the effects of the bonded rapid maxillary expander (RME) alone compared with RME with lip bumper (LB) treatment on the mandibular transverse changes. METHODS: This retrospective study analyzed 3 groups: the control group with no orthodontic or orthopedic treatment (23 patients [14 females, 9 males]; mean age 9.13 years at T1 and 11.24 years at T2); the RME group with no mandibular treatment (22 patients [9 females, 13 males]; mean age 8.73 years at T1 and 12.04 years at T2); and RME + LB group (23 patients [16 females, 7 males]; mean age 9.45 years at T1 and 12.18 years at T2). Three-dimensional superimposition of the mandibular images was performed with cone-beam computed tomography taken at prephase and postphase I treatment (growth and development check records for the control group) to conduct the angular and linear measurements at the dental, alveolar, and skeletal levels. The intergroup comparisons were performed using the Mann-Whitney U-test. RESULTS: Accompanying slight molar self-uprighting during the normal mandibular growth period observed in the control group, transverse growth was also observed in both alveolar and basal bone levels of the mandible, but no significant changes in the alveolar bone inclination occurred. The bonded RME slightly increased the mandibular first molar uprighting but not the mandibular widths at the tooth or alveolar levels. Adding a LB significantly increased the intermolar width and molar uprighting while decreasing the alveolar bone inclination but did not increase the amount of mandibular transverse growth at the bone level. CONCLUSIONS: RME alone did not significantly increase the transverse dimension of the mandible. RME + LB significantly increased mandibular intermolar width, uprighted the mandibular molars, and reduced the alveolar bone inclination.

Traditional plant functional groups explain variation in economic but not size-related traits across the tundra biome.

AIM: Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. LOCATION: Tundra biome. TIME PERIOD: Data collected between 1964 and 2016. MAJOR TAXA STUDIED: 295 tundra vascular plant species. METHODS: We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits. RESULTS: Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression. MAIN CONCLUSIONS: Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra vegetation change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insights for ecological prediction and modelling.

Nicotinic acid effects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro study.

Our aim was to characterize the effects and the underlying mechanisms of the lipid-regulating agent Niaspan(®) on both insulin action and triglyceride decrease in 20 nondiabetic, dyslipidemic men with metabolic syndrome receiving Niaspan(®) (2 g/day) or placebo for 8 weeks in a randomized, cross-over study. The effects on plasma lipid profile were characterized at the beginning and the end of each treatment period; insulin sensitivity was assessed using the 2-step euglycemic hyperinsulinemic clamp and VLDL-triglyceride turnover by measuring plasma glycerol enrichment, both at the end of each treatment period. The mechanism of action of nicotinic acid was studied in HuH7 and mouse primary hepatocytes. Lipid profile was improved after Niaspan(®) treatment with a significant-28% decrease in triglyceride levels, a+17% increase in HDL-C concentration and unchanged levels of fasting nonesterified fatty acid. VLDL-tri-glyceride production rate was markedly reduced after Niaspan(®) (-68%). However, the treatment induced hepatic insulin resistance, as assessed by reduced inhibition of endogenous glucose production by insulin (0.7±0.4 vs. 1.0±0.5 mg/kg · min, p<0.05) and decrease in fasting hepatic insulin sensitivity index (4.8±1.8 vs. 3.2±1.6, p<0.05) in the Niaspan(®) condition. Nicotinic acid also reduced insulin action in HuH7 and primary hepatocytes, independently of the activation of hepatic PKCε. This effect was associated with an increase in diacylglycerol and a decrease in tri-glyceride contents that occurred in the absence of modification of DGAT2 expression and activity. Eight weeks of Niaspan(®) treatment in dyslipidemic patients with metabolic syndrome induce hepatic insulin resistance. The mechanism could involve an accumulation of diacylglycerol and an alteration of insulin signaling in hepatocytes.

Unlocking ground-based imagery for habitat mapping.

Fine-grained environmental data across large extents are needed to resolve the processes that impact species communities from local to global scales. Ground-based images (GBIs) have the potential to capture habitat complexity at biologically relevant spatial and temporal resolutions. Moving beyond existing applications of GBIs for species identification and monitoring ecological change from repeat photography, we describe promising approaches to habitat mapping, leveraging multimodal data and computer vision. We illustrate empirically how GBIs can be applied to predict distributions of species at fine scales along Street View routes, or to automatically classify and quantify habitat features. Further, we outline future research avenues using GBIs that can bring a leap forward in analyses for ecology and conservation with this underused resource.

Mandibular alveolar bone thickness in untreated Class I subjects with different vertical skeletal patterns: a cone-beam computed tomography study.

OBJECTIVE: To evaluate the mandibular alveolar bone thickness in untreated skeletal Class I subjects with different vertical skeletal patterns. MATERIALS AND METHODS: A total of 50 preorthodontic treatment cone-beam computed tomography (CBCT) images of a skeletal Class I Chinese population with near-normal occlusion were selected. The buccal and lingual alveolar bone thicknesses of mandibular canines to second molars were measured at 2 mm below the cementoenamel junction (CEJ), mid-root, and root apex levels. Differences in the measurements were analyzed with Mann-Whitney U-test. The correlation between alveolar bone thickness and the sella-nasion-mandibular plane (SN-MP) angle was calculated using Pearson correlation coefficients and linear regression analysis. RESULTS: Buccal alveolar bone was thinner on all mandibular canines to first molars but thicker on second molars in comparison with lingual alveolar bone. Buccal alveolar bone was within 1 mm at the levels of 2 mm below CEJ and mid-root for the canines and first premolars. Significant differences were detected among subjects with different vertical patterns, with a negative correlation between the SN-MP angle and alveolar thickness, especially in the canine and premolar regions. The thinnest buccal and lingual alveolar bone were detected in the high-angle group canine region (0.50 mm at the levels of 2 mm below CEJ and mid-root for the buccal side, 0.90 mm at the level of 2 mm below the CEJ for the lingual side). CONCLUSIONS: To avoid periodontal complications, buccal-lingual movement of the mandibular canines and first premolars should be limited, especially in high-angle patients.

Correlation between TMJ Space Alteration and Disc Displacement: A Retrospective CBCT and MRI Study.

This study aims to determine if a large anterior and reduced posterior/superior joint space is highly predictable for disc displacement. From patients with temporomandibular disorders symptoms, fifty-two experimental joints and fourteen control joints were included. The cone beam computed tomography (CBCT) images were used to calculate posterior-to-anterior (P-A) and superior-to-anterior (S-A) joint space ratios, while disc position was determined using magnetic resonance imaging (MRI). One-way analysis of covariance test and receiver operating characteristics analysis were carried out. The results showed that among the 52 experimental joints, 45 were diagnosed as disc displacement and 7 as normal disc positions (N). All 14 control joints showed normal disc positions. The P-A ratio was 1.46 ± 0.21, 0.99 ± 0.23, and 0.86 ± 0.30 in the control, N, and DD groups, respectively (p < 0.001). The S-A ratio was 1.80 ± 0.27, 1.44 ± 0.33, and 1.08 ± 0.35 in the control, N, and DD groups, respectively (p < 0.001). When an altered P-A ratio and/or S-A ratio are observed on the CBCT, the diagnosis of disc displacement is quite predictable with high sensitivity and specificity.

Buccolingual Inclination of Second Molars in Untreated Adolescents and Adults with Near Normal Occlusion: A CBCT Study.

The mandibular second molars are lingually positioned relative to the alveolar ridge and have a limited amount of lingual alveolar bony support. As the maxillary second molars are articulated with the mandibular second molars, maintaining the normal buccolingual inclination of both maxillary and mandibular second molars would potentially help to not only optimize the masticatory function, but also avoid dehiscence and fenestration. The current study evaluated the buccolingual inclination of second molars in untreated adolescents and adults. One hundred and two Caucasian subjects with skeletal class I and minimum dental arch crowding/spacing were selected and divided into two groups: (1) adolescent group: age 12-18 years, N = 51 (21 females, 30 males); (2) adult group: age 19-65 years, N = 51 (40 females, 11 males). For each subject, the inclination for each second molar was measured as the angle between the long axis of each tooth and a vertical line on cone beam computed tomography images. The Mann-Whitney U test was used for intergroup comparisons. Maxillary second molars exhibited a buccal inclination of 15.30° in the adolescent group and 15.70° in the adult group. Mandibular second molars exhibited a lingual inclination of 17.05° in the adolescent group and 15.20° in the adult group. No statistically significant differences were detected between the age groups. In addition, a statistically significant difference was only found between genders in the adolescent group for the maxillary second molar inclination. In summary, maxillary second molars exhibited buccal inclination and mandibular second molars exhibited lingual inclination. The amount of buccolingual inclination of the second molars was similar in the adolescent and adult groups.

Lip Bumper Therapy Does Not Influence the Sagittal Mandibular Incisor Position in a Retrospective CBCT Study.

Lip bumper (LB) therapy is used as a treatment approach for mild to moderate crowding without extraction of teeth. Previous studies demonstrated that LB increases arch length through molar uprighting and lateral expansion. However, the effects of LB on mandibular incisors are inconclusive. The controversial results from different studies may be due to limitations including absence of a control group and/or use of 2D radiography. To address this issue, the current retrospective longitudinal CBCT study compared a rapid maxillary expansion (RME) group with no lower treatment [16 patients (9 females, 7 males); median age 8.86 years at T1 and 11.82 years at T2] and an RME + LB group [18 patients (13 females, 5 males); median age 9.46 years at T1 and 12.10 years at T2]. The CBCTs taken before and after phase 1 treatment were 3D superimposed based on the mandibular structure and were measured to determine the angular and linear changes of the mandibular incisors over the course of LB treatment. For comparisons between different timepoints within a group, a Wilcoxon matched-pairs signed rank test was used. For intergroup comparisons, a Mann-Whitney U test was used. Both groups showed eruption and protrusion of the mandibular incisors during the observation period, while there was no significant change in proclination of the lower incisors. When comparing the discrepancy of change between groups, there was no statistically significant difference detected. In summary, by utilizing a longitudinal 3D database, the current study demonstrated that the effect of LB on the position of the mandibular incisors is limited.

Estimating cost-offsets of new medications: use of new antipsychotics and mental health costs for schizophrenia.

Estimation of the effect of one treatment compared to another in the absence of randomization is a common problem in biostatistics. An increasingly popular approach involves instrumental variables-variables that are predictive of who received a treatment yet not directly predictive of the outcome. When treatment is binary, many estimators have been proposed: method-of-moments estimators using a two-stage least-squares procedure, generalized-method-of-moments estimators using two-stage predictor substitution or two-stage residual inclusion procedures, and likelihood-based latent variable approaches. The critical assumptions to the consistency of two-stage procedures and of the likelihood-based procedures differ. Because neither set of assumptions can be completely tested from the observed data alone, comparing the results from the different approaches is an important sensitivity analysis. We provide a general statistical framework for estimation of the casual effect of a binary treatment on a continuous outcome using simultaneous equations to specify models. A comparison of health care costs for adults with schizophrenia treated with newer atypical antipsychotics and those treated with conventional antipsychotic medications illustrates our methods. Surprisingly large differences in the results among the methods are investigated using a simulation study. Several new findings concerning the performance in terms of precision and robustness of each approach in different situations are obtained. We illustrate that in general supplemental information is needed to determine which analysis, if any, is trustworthy and reaffirm that comparing results from different approaches is a valuable sensitivity analysis.

Short-term and long-term effects of rapid maxillary expansion on the nasal soft and hard tissue.

OBJECTIVES: To evaluate nasal soft and hard tissue changes immediately post-rapid maxillary expansion (RME) and to assess the stability of these changes using cone beam computed tomography (CBCT). MATERIALS AND METHODS: A total of 35 treatment group (TG) patients (18 girls, 17 boys; 9.39 ± 1.4) had a pre-RME CBCT and a post-RME CBCT approximately 66 days after expansion, and 25 patients had a follow-up CBCT 2.84 years later. A total of 28 control group (CG; no RME) patients (16 girls, 12 boys; 8.81 ± 1.6) had an initial CBCT and a CBCT an average of 2.25 years later. Soft and hard tissue nasal landmarks were measured in transverse, sagittal, and coronal planes of space on CBCT scans. Differences within the same group were evaluated by paired t-tests or Wilcoxon signed-rank tests. Long-term comparisons between TG and CG were evaluated by independent-sample t-tests or Wilcoxon rank-sum tests. RESULTS: Immediately post-RME, there were statistically significant mean increases of 1.6 mm of alar base width, 1.77 mm of pyriform height, and 3.57 mm of pyriform width (P < .05). CG showed the significant increases over 2.25 years (P < .001). Compared with CG, the long-term evaluation of TG demonstrated only pyriform height and pyriform width showed a statistically significant difference (P < .01). CONCLUSIONS: Although RME produced some significant increase on the nasal soft tissue immediately after expansion, it regressed to the mean of normal growth and development over time. However, long-term evaluation of TG compared with CG showed only pyriform height and pyriform width to be affected by RME.

Global plant trait relationships extend to the climatic extremes of the tundra biome.

The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.

A dietary flavone confers communicable protection against colitis through NLRP6 signaling independently of inflammasome activation.

Flavones represent a class of polyphenols that are found in many plant-derived food sources. Herein, we provide evidence that the anti-inflammatory and antiproliferative effect of the flavone apigenin relies on the regulation of the gut microbiota by the NOD-like receptor family pyrin domain containing 6 (Nlrp6). When challenged by dextran sulfate sodium (DSS) in drinking water, mice were protected against colitis upon cohousing with apigenin-treated animals. In contrast, the protective effect was lost in the absence of Nlrp6. Sequencing of the 16S ribosomal RNA gene revealed a shift in the composition of the gut microbiota in apigenin-treated mice that was not observed in the absence of Nlrp6. Equally important, we find that the antiproliferative effect of apigenin was dominantly transmitted after cohousing, while being compromised in Nlrp6-deficient mice. In contrast, the symptoms of colitis were alleviated upon apigenin administration even in the absence of either caspase-1/11 or Asc. Collectively, these data indicate that apigenin modulated an inflammasome-independent mechanism by which Nlrp6 reprograms the gut microbiota for protecting mice against colitis. Our study highlights a modulation of the Nlrp6 signaling pathway by a prominent constituent of the human diet that may point toward improved ways to treat inflammatory bowel diseases.

Comparison of two methods of measuring wood pyrolysis tar.

Two methods for the sampling and analysis of tar produced from wood pyrolysis were compared. The first method used a conventional cold-trapping technique in solvent-filled impingers followed by liquid injection. The second one is a new application of multibed solid-phase adsorbent (SPA) tubes followed by thermal desorption (TD). Both methods are based on gas chromatography (GC) coupled with mass spectrometry (MS). Quantification was performed with a well reproducible GC-MS method with three internal deuterated standards. The SPA/TD method offers several advantages. No solvent is required, the detection levels are improved, and gas chromatography separation is easier. Moreover, sampling time is reduced from about 1h (for the conventional cold-trapping technique in impingers) to a few seconds. No discrimination was observed between the two sampling methods for the 10 quantified compounds (aromatic compounds from benzene to phenanthrene and phenols) except for benzene.

Comparison of use of medications after acute myocardial infarction in the Veterans Health Administration and Medicare.

BACKGROUND: There is concern that care provided in the Veterans Health Administration (VA) may be of poorer quality than non-VA health care. We compared use of medications after acute myocardial infarction in the VA with that in non-VA healthcare settings under fee-for-service (FFS) Medicare financing. METHODS AND RESULTS: We used clinical data from 2486 VA and 29 249 FFS men >65 years old discharged with a confirmed diagnosis of acute myocardial infarction from 81 VA hospitals and 1530 non-VA hospitals. We reported odds ratios (ORs) for use of thrombolytics, beta-blockers, ACE inhibitors, or aspirin among ideal candidates adjusted for age, sample design (hospital academic affiliation, availability of cardiac procedures, and volume), and within-hospital clustering. Ideal VA candidates were more likely to undergo thrombolytic therapy at arrival (OR [VA relative to Medicare] 1.40 [1.05, 1.74]) or to receive ACE inhibitors (OR 1.67 [1.12, 2.45]) or aspirin (OR 2.32 [1.81, 3.01]) at discharge and equally likely to receive beta-blockers (OR 1.09 [1.03, 1.40]) at discharge. CONCLUSIONS: Ideal candidates in VA were at least as likely as those in FFS to receive medical therapies of known benefit for acute myocardial infarction.

Trends in the use of drug therapies in patients with acute myocardial infarction: 1988 to 1992.

OBJECTIVES: In this study, we investigated the use of thrombolytic agents and other cardiac drugs in a national cohort of patients with acute myocardial infarction and assessed the influence of large clinical studies on types of thrombolytic therapy prescribed. BACKGROUND: Information about usage patterns for these drugs is unavailable, and little is known about the impact of large clinical trials on their use. METHODS: We conducted a retrospective cohort study of 65,011 patients who were treated for acute myocardial infarction during fiscal years 1988 to 1992 (October 1, 1987 to September 30, 1992) in hospitals participating in the SMS Corporation's on-line data pool. RESULTS: The overall thrombolysis rate for patients with acute myocardial infarction increased from 11% in fiscal year 1988 to 18% in fiscal year 1990 and has remained approximately at that level since then. In mid-1989, tissue plasminogen activator was used in 90% of the patients receiving thrombolysis, whereas streptokinase was used in only 10%. Since 1991, tissue plasminogen activator has been used in 60% of patients and streptokinase in almost 30%. Much of this change came after presentation and publication of results of the Second Gruppo Italiano per lo Studio Della Sopravvivenza nell'Infarto Miocardico (GISSI-2) and the Third International Study of Infarct Survival (ISIS-3) trials. Over these 5 years, use of beta-adrenergic blocking agents increased steadily, and use of calcium-channel blocking agents declined steadily. CONCLUSIONS: Current usage rates of thrombolytic therapy are lower than expected, but trends in usage rates for beta-blockers and calcium channel blockers reflect their increasing and decreasing approval, respectively. Presentation and publication of results from the Third International Study of Infarct Survival and the Second Gruppo Italiano per lo Studio Della Sopravvivenza nell'Infarto Miocardico trials appear to have influenced the type of thrombolytic agent prescribed.

Managing the care of schizophrenia. Lessons from a 4-year Massachusetts Medicaid study.

BACKGROUND: In 1992, Massachusetts launched a state-wide managed care plan for all Medicaid beneficiaries. METHODS: This retrospective, multi-year, cross-sectional study used administrative data from the Massachusetts Division of Medical Assistance and Department of Mental Health, consisting of claims for 16,400 disabled adult patients insured by Medicaid in Massachusetts between July 1, 1990, and June 30, 1994. The main outcome measures include annual rates of hospitalization, emergency department utilization, and follow-up care 30 days after discharge; length of inpatient stay; and per-person inpatient and outpatient expenditures. RESULTS: Between 1991 and 1994, the likelihood of an inpatient admission decreased from 29% to 24% and was accompanied by a slight reduction in length of stay (median number of bed-days per admission dropped by 3.3 days). There was a slight decrease in the number of patients who sought care in general hospital emergency department utilization. However, there was a small increase in the fraction of patients readmitted within 30 days of discharge. Medicaid and Department of Mental Health expenditures for mental health per treated beneficiary decreased slightly, from $11,060 to $10,640, during the 4-year study period. CONCLUSION: Although per-person expenditures dropped and most patient patterns of care remained the same, longer-term study is recommended to asses whether the trends can be maintained.

Hypersensitivity to insulin during remissions in cyclosporin-treated IDDM patients.

OBJECTIVE: To test the sensitivity to insulin in recent-onset IDDM patients, its course according to treatment, and the advent of remissions. RESEARCH DESIGN AND METHODS: The euglycemic hyperinsulinemic clamp was used in 54 recent-onset IDDM patients and 14 healthy control subjects. Patients were tested after 1,2, and 4 wk of treatment with either insulin or insulin plus cyclosporin A, during cyclosporin A-associated long-lasting remissions, and during relapses. RESULTS: Insulin sensitivity was markedly decreased in all patients at onset. It was rapidly restored by insulin therapy, whether immunosuppression was associated with it or not. Insulin sensitivity was even higher than normal in the remission patients, who also were characterized by the reappearance of some endogenous insulin secretion and the sustained normalization of blood glucose profiles. During relapses, the deterioration of the blood glucose profiles was associated with some loss of insulin sensitivity. CONCLUSIONS: Cyclosporin A-associated remissions represent an original situation that associates euglycemia with the persistence of low endogenous insulin secretion. Cyclosporin A by itself had no influence on sensitivity to insulin, but allowed the reappearance of some insulin secretory capacity that contributed, with the improvement of insulin sensitivity, to the development of the diabetes honeymoon. The secretion of endogenous insulin, although lower than normal, was sufficient to secure a high sensitivity to insulin and the maintenance of normal blood glucose profiles, presumably because of the fact that insulin was released directly into the portal vein in these conditions. This metabolic state was precarious: the optimal sensitivity to insulin disappeared in patients who relapsed. These results have important clinical consequences: the preservation of islet residual secretory capacity by the use of newer nontoxic immunosuppressive protocols, combined with a minimal supportive insulin therapy in remission patients, may prolong remissions and maintain an optimal insulin sensitivity.

Plasma glucose kinetics and response of insulin and GIP following a cereal breakfast in female subjects: effect of starch digestibility.

BACKGROUND/OBJECTIVES: Foods with high contents of slowly digestible starch (SDS) elicit lower glycemic responses than foods with low contents of SDS but there has been debate on the underlying changes in plasma glucose kinetics, that is, respective contributions of the increase in the rates of appearance and disappearance of plasma glucose (RaT and RdT), and of the increase in the rate of appearance of exogenous glucose (RaE) and decrease in endogenous glucose production (EGP). SUBJECTS/METHODS: Sixteen young healthy females ingested in random order four types of breakfasts: an extruded cereal (0.3% SDS: Lo-SDS breakfast) or one of three biscuits (39-45% SDS: Hi-SDS breakfasts). The flour in the cereal products was labeled with (13)C, and plasma glucose kinetics were measured using [6,6-(2)H2]glucose infusion, along with the response of plasma glucose, insulin and glucose-dependent insulinotropic peptide (GIP) concentrations. RESULTS: When compared with the Lo-SDS breakfast, after the three Hi-SDS breakfasts, excursions in plasma glucose, the response of RaE, RaT and RdT, and the reduction in EGP were significantly lower (P<0.05). The amount of exogenous glucose absorbed over the 4.5-h postprandial period was also significantly lower by ~31% (P<0.001). These differences were associated with lower responses of GIP and insulin concentrations. CONCLUSIONS: Substituting extruded cereals with biscuits slows down the availability of glucose from the breakfast and its appearance in peripheral circulation, blunts the changes in plasma glucose kinetics and homeostasis, reduces excursions in plasma glucose, and possibly distributes the glucose ingested over a longer period following the meal.

Effects of ketone bodies on basal and insulin-stimulated glucose utilization in man.

Using the euglycemic clamp technique, we investigated the effects of high ketone body levels on basal and insulin-stimulated glucose utilization in normal subjects. Infusion of sodium acetoacetate in the postabsorptive state raised ketone body levels from 150 +/- 20 (+/- SE) mumol/liter to more than 1 mmol/liter. Endogenous glucose production declined from 2.71 +/- 0.20 mg kg-1 min-1 to 1.75 + 0.26 (P less than 0.01) and glucose utilization from 2.71 +/- 0.20 to 1.98 +/- 0.17 mg kg-1 min-1 (P less than 0.01), while blood glucose was maintained at the initial level by the infusion of glucose. There were no changes in plasma glucagon, insulin, or C-peptide. Plasma nonesterified fatty acids (P less than 0.01) and blood glycerol (P less than 0.01) and alanine (P less than 0.05) decreased, while blood lactate increased (P less than 0.01). Infusion of sodium bicarbonate had no effect on glucose kinetics. The decreases in glucose utilization and endogenous glucose production during the infusion of acetoacetate were not modified when the fall of plasma nonesterified fatty acids was prevented by iv heparin injection. During control euglycemic hyperinsulinemic clamps (1 and 10 mU kg-1 min-1 insulin infusion), endogenous glucose production was suppressed at the lowest insulin infusion rate; glucose utilization increased first to 7.32 +/- 0.96 mg kg-1 min-1 and then to 16.5 +/- 1.27 mg kg-1 min-1. During euglycemic hyperinsulinemic clamps with simultaneous sodium acetoacetate infusion, similar insulin levels were attained; endogenous glucose production was also suppressed at the lowest insulin infusion rate, and insulin-stimulated glucose utilization rates (7.93 +/- 1.70 and 15.80 +/- 1.30 mg kg-1 min-1) were not modified. In conclusion, acetoacetate infusion decreased basal, but not insulin-stimulated, glucose utilization. The increase in lactate during acetoacetate infusion in the postabsorptive state suggests that ketone body acted by decreasing pyruvate oxidation.