Systematic review of the impact of osteoarthritis on health outcomes for comorbid disease in older people.

OBJECTIVE: A systematic review was undertaken examining the impact of comorbid osteoarthritis on health outcomes for people aged 50 years or older with cardiovascular disease, diabetes or obesity. DESIGN: The protocol is registered in PROSPERO (CRD42015023417). Relevant electronic databases and grey literature were systematically searched for studies published in English between January 2005 and December 2016. Two reviewers independently screened studies for selection using predetermined inclusion and exclusion criteria, and independently completed methodological quality review. Data was extracted at study level by one reviewer and independently checked by a second reviewer, using a standardized form. The results across studies were qualitatively synthesized with outcomes described and summarized. RESULTS: Of 1456 articles, we identified 15 relevant studies, with nine good to high quality studies describing significant negative impact of osteoarthritis on outcomes for cardiovascular diseases. There were too few studies focussing on diabetes and obesity to make conclusions in regard to these diseases. CONCLUSIONS: This review provides evidence that osteoarthritis should not be overlooked when impacts of chronic disease on health outcomes and related health service use are considered. There is a clear need for more studies that consider the impacts of osteoarthritis on comorbid disease, especially those that consider the impact of osteoarthritis beyond the morbidity impacts. The management of comorbid osteoarthritis should be addressed for those with cardiovascular disease, and treatment choices considered given this association.

A Systematic Review of Clinical Practice Guidelines for Identification and Management of Frailty.

OBJECTIVE: This study aims to appraise and summarize consistent recommendations from clinical practice guidelines (CPGs) for identification and management of frailty to maintain and improve functional independence of elderly population. METHODS: A systematic search of Ovid MEDLINE, Embase, PubMed, PsycINFO, and CINAHL electronic databases using database-specific search terms in two broad areas "guidelines" and "frailty", and a manual search of websites with the key phrase "frailty guideline" was performed. The inclusion criteria included CPGs focusing on identifying and managing frailty in population >65 years old, published in English since January 2010. Three reviewers independently assessed guideline quality using the AGREE II instrument. Data extraction was performed, followed by compilation and comparison of all recommendations to identify the key consistent recommendations. RESULTS: Six CPGs met the inclusion criteria; however, only three CPGs had high methodological quality in accordance with AGREE II appraisal. The average AGREE II scores of all six CPGs were: 84.5%, 68%, 46.5%, 81.5%, 56.3%, and 60.2% for domains 1-6 (scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability, and editorial independence) respectively. A total of 54 recommendations were identified, with 12 key recommendations suggested frequently by the CPGs. CONCLUSION: The AGREE II instrument identified strengths and weaknesses of the CPGs, but failed to assess clinical implications and feasibility of the guidelines. Further research is needed to improve clinical relevance of CPGs in the identification and management of frailty. The feasibility in implementing these guidelines with regards to cost-effectiveness of frailty screening warrants further investigation.

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

Osteoporosis and gait and balance disturbances in older sarcopenic obese New Zealanders.

UNLABELLED: Bone, muscle, and fat may affect gait and balance in older adults. Osteoporosis was prevalent in low muscle mass participants and related to gait and balance deficits. Low muscle combined with high fat mass had more functional deficits and poorer bone health, which has implications for falls risk and fractures. INTRODUCTION: Decreasing bone density and muscle mass and increasing fat mass may act synergistically to affect gait and balance in older adults. METHODS: One hundred eighty-three older adults (age 72.7 +/- 6 years, range 56-93; body mass index 28.2 +/- 4.9, range 16.6-46.0) were recruited from a New Zealand falls prevention intervention trial. Total and appendicular skeletal muscle mass (ASM), percent fat, and bone mineralization were assessed by dual energy X-ray absorptiometry and used to characterize normal lean (NL, n = 51), sarcopenic (SS, n = 18), sarcopenic obese (SO, n = 29), and obese (OO, n = 85) phenotypes. Functional performance was assessed using timed up and go, chair stand, single leg stand, and step test. Regression models were adjusted for age, sex, medications, and physical activity. RESULTS: Femoral neck osteoporosis was present in 22% SS, 17% SO, 12% NL, and 7% OO. Femoral neck osteoporosis with low ASM predicted poor chair stand performance (beta -3.3, standard error 1.6, p = 0.04). SO scored lowest on the chair stand (p = 0.03) and step test (p = 0.03). Higher ASM predicted faster timed up and go performance (p = 0.001). CONCLUSIONS: Osteoporosis was prevalent in low ASM groups (SS and SO) and related to gait and balance deficits, particularly in the SO. This has implications for falls risk, fractures, and interventions.

Sex-specific muscle and metabolic biomarkers associated with gait speed and cognitive transitions in older adults: a 9-year follow-up.

Physical frailty and cognitive frailty share biological mechanisms, but sex-specific biomarkers associated with transitions in gait speed and cognition during ageing are poorly understood.Gait speed, cognition (3MSE), body composition (DXA) and serological biomarkers were assessed annually over 9 years in 216 males (72.7 + 8.07 years) and 384 females (71.1 + 8.44 years). In females, maintaining normal gait speed was associated with lower percent body fat (IRR 0.793, p = 0.001, 95%CI 0.691-0.910) and lower lactate dehydrogenase (LDH) (IRR 0.623, p = 0.00, 95%CI 0.514-0.752), and in males, the association was with higher cholesterol (IRR 1.394, p = 0.001, 95%CI 1.154-1.684). Abnormal to normal gait speed transitions were associated with higher insulin in females (IRR 1.325, p = 0.022, 95%CI 1.041-1.685) and lower creatinine in males (IRR 0.520, p = 0.01, 95%CI 0.310-0.870). Normal to slow gait speed transitions in males were associated with IGF-1 (IRR 1.74, p = 0.022, 95%CI 1.08-2.79) and leptin in females (IRR 1.39, p = 0.043, 95%CI 1.01-1.91.) Maintaining normal cognition was associated with lower LDH in females (IRR 0.276, p = 0.013, 95%CI 0.099-0.765) and higher appendicular skeletal muscle mass in males (IRR 1.52, p = 0.02, 95%CI 1.076-2.135). Improved cognition was associated with higher leptin (IRR 7.5, p = 0.03, 95%CI 1.282-44.34) and lower triglyceride (IRR 0.299, p = 0.017, 95%CI 0.110-0.809) in males. Education was protective against cognitive decline in females (IRR 0.84, p = 0.037, 0.732-0.982). Sex-specific biomarkers of muscle (LDH, Creatinine, IGF-1, APSM) and metabolism (%fat, insulin,cholesterol, leptin, tryglycerides) were associated with gait speed and cognitive transitions. These data suggest that modifiable biomarkers of muscle and metabolism could be targeted for interventions.

Betaine aldehyde dehydrogenase in plants.

Plant betaine aldehyde dehydrogenases (BADHs) have been the target of substantial research, especially during the last 20 years. Initial characterisation of BADH as an enzyme involved in the production of glycine betaine (GB) has led to detailed studies of the role of BADH in the response of plants to abiotic stress in vivo, and the potential for transgenic expression of BADH to improve abiotic stress tolerance. These studies have, in turn, yielded significant information regarding BADH and GB function. Recent research has identified the potential for BADH as an antibiotic-free marker for selection of transgenic plants, and a major role for BADH in 2-acetyl-1-pyrroline-based fragrance associated with jasmine and basmati style aromatic rice varieties.

Relationship of Incident Falls with Balance Deficits and Body Composition in Male and Female Community-Dwelling Elders.

OBJECTIVE: Sarcopenia and obesity are reported risk factors for falls, although the data are not consistent and most studies do not make sex comparisons. We investigated whether falls were associated with balance, gait, and body composition, and whether these relationships are sex-specific. DESIGN: Secondary analysis of 4-year follow-up data from of the New Mexico Aging Process Study. SETTING: Albuquerque, New Mexico. PARTICIPANTS: 307 participants (M, n=122, 75.8 yr. SD5.5; F, n=183, 74.6yr SD6.1). MEASUREMENTS: Gait and balance were assessed annually using the Tinetti test. Lean body mass (LBM), appendicular skeletal muscle mass (ASM), fat free mass (FFM), total fat mass (FM) were assessed annually by DXA. Falls were assessed using bimonthly falls calendars. Hazard ratios (HR) for 2-point worsening in gait and balance score and falls were calculated by Cox proportional hazard for men and women. RESULTS: Baseline balance deficits, and not body composition, represented the strongest predictor of falls. For the total balance score, the variables with significant sex interactions were ASM (Male-HR 1.02 95%CI 0.60-1.73; Female-HR 1.92 95%CI 1.05-3.52, p=0.03) and FFM (Male-HR 1.04 95%CI 0.64-1.70; Female-HR 1.91 95%CI 1.12-3.24, p=0.04), after adjustment for age, sarcopenia and physical activity. The body composition relationship with balance deficits was U-shaped with the strongest predictors being low LBM in males and high FM in females. CONCLUSIONS: Specific body composition components and balance deficits are risk factors for falls following sex-specific patterns. Sex differences need to be explored and considered in interventions for worsening balance and falls prevention.

Establishing an Operational Definition of Sarcopenia in Australia and New Zealand: Delphi Method Based Consensus Statement.

BACKGROUND: Globally there are several operational definitions for sarcopenia, complicating clinical and research applications. OBJECTIVE: The objective of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Task Force on Diagnostic Criteria for Sarcopenia was to reach consensus on the operational definition of sarcopenia for regional use by clinicians and researchers. METHOD: A four-Phase modified Delphi process was undertaken in which 24 individuals with expertise or a recognised interest in sarcopenia from different fields across Australia and New Zealand were invited to be Task Force members. An initial face-to-face meeting was held in Adelaide, South Australia, in November 2017, followed by two subsequent online Phases conducted by electronic surveys. A final Phase was used to approve the final statements. Responses were analysed using a pre-specified strategy. The level of agreement required for consensus was 80%. RESULTS: In Phase 2, 94.1% of Task Force respondents voted in favour of adopting an existing operational definition of sarcopenia. In Phase 3, 94.4% of respondents voted in favour of adopting the European Working Group on Sarcopenia in Older People (EWGSOP) definition as the operational definition for sarcopenia in Australia and New Zealand. CONCLUSION: With consensus achieved, the ANZSSFR will adopt, promote and validate the EWGSOP operational definition of sarcopenia for use by clinicians and researchers in Australia and New Zealand.

Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

Designing Drug Trials for Frailty: ICFSR Task Force 2018.

To reduce disability and dependence in older adults, frailty may represent an appropriate target for intervention. While preventing frailty through lifestyle interventions may be the optimal public health approach for many population groups, pharmacological approaches will likely be needed for individuals who meet frailty criteria or who have comorbid conditions that contribute to and complicate the frailty syndrome, and for those who are not compliant with lifestyle interventions. Barriers to successful development of drug treatments for frailty include variability in how the frailty syndrome is defined, lack of agreement on the best diagnostic tools and outcome measures, and the paucity of sensitive, reliable, and validated biomarkers. The International Conference on Frailty and Sarcopenia Research Task Force met in Miami, Florida, on February 28, 2018, to consider the status of treatments under development for frailty and discuss potential strategies for advancing the field. They concluded that at the present time, there may be a more productive regulatory pathway for adjuvant treatments or trials targeting specific functional outcomes such as gait speed. They also expressed optimism that several studies currently underway may provide the insight needed to advance drug development for frailty.

International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management.

OBJECTIVES: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). METHODS: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit-harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. RECOMMENDATIONS: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

Behaviors underlying the use of nonvitamin nonmineral dietary supplements in a healthy elderly cohort.

OBJECTIVE: The purpose of the study was to examine factors underlying the decision to use nonvitamin, nonmineral (NVNM) dietary supplements in a healthy elderly cohort. DESIGN: Questionnaires were administered to probe for perceived health status, health insurance coverage, income level, monthly expenditure for supplements, duration of supplement use, information source, disclosure of supplement taking to physician, reasons for NVNM supplements use and perceived benefits, use of supplements to replace or complement a medication, and usual purchasing place. SETTING/PARTICIPANTS: Between 1999- 2001, 418 elderly males (34.7%) and females (65.3%) ages 60-96 years were surveyed. RESULTS: Nonvitamin nonmineral supplement "consumers" and "non-consumers" were not significantly different for sex, age, ethnicity, perceived health status, income level, and health insurance access. The average consumer took three NVNM supplements and spent significantly more money on supplements than non-consumers (p < 0.001). Over 44% of consumer's responses indicated that they had been using NVNM supplements for over 2 years. Literature/media were predominately the source of information with mail order being the most frequent method of purchase. Over 39% of consumer's responses showed that supplement use was revealed to a physician. Arthritis, memory improvement, and general health and well-being were the main reasons to use NVNM supplements. Less joint pain/improved mobility was the main perceived improvement from taking NVNM supplements. Overall, over 53% of consumer's responses showed that no change was noticed from taking NVNM supplements. CONCLUSIONS: Although the most commonly reported responses by those noticing change from NVNM supplement use were improved mobility and less joint pain, over half of the responses indicated that they did not feel any benefit from taking supplements, yet continued to purchase and take them. Communication of NVNM supplement use to their physician was low. More studies are needed to investigate what influences the decision to continue supplement use regardless of the lack of efficacy, considerable cost, and potential risks.

Reversible States of Physical and/or Cognitive Dysfunction: A 9-Year Longitudinal Study.

OBJECTIVES: To determine 1) age-adjusted transition probabilities to worsening physical/cognitive function states, reversal to normal cognition/physical function, or maintenance of normal state; 2) whether these transitions are modulated by sex, BMI, education, hypertension (HTN), health status, or APOE4; 3) whether worsening gait speed preceded cognition change, or vice versa. DESIGN: Analysis of 9-year prospective cohort data from the New Mexico Aging Process Study. SETTING: Healthy independent-living adults. PARTICIPANTS: 60+ years of age (n= 598). MEASUREMENTS: Gait speed, cognitive function (3MSE score), APOE4, HTN, BMI, education, health status. RESULTS: Over 9 years, 2129 one-year transitions were observed. 32.6% stayed in the same state, while gait speed and cognitive function (3MSE scores) improved for 38% and 43% of participants per year, respectively. Transitions to improved function decreased with age (P< 0.001), APOE4 status (P=0.02), BMI (P=0.009), and health status (P=0.009). Transitions to worse function were significantly increased for the same factors (all P<0.05). Times to lower gait speed and cognitive function did not precede each other (P=0.91). CONCLUSIONS: Transitions in gait speed and cognition were mutable with substantial likelihood of transition to improvement in physical and cognitive function even in oldest-old, which may have clinical implications for treatment interventions.

Arbuscular mycorrhizal fungi: effects on plant terpenoid accumulation.

Arbuscular mycorrhizal fungi (AMF) are a diverse group of soil-dwelling fungi that form symbiotic associations with land plants. AMF-plant associations promote the accumulation of plant terpenoids beneficial to human health, although how AMF mediate terpenoid accumulation is not fully understood. A critical assessment and discussion of the literature relating to mechanisms by which AMF influence plant terpenoid accumulation, and whether this symbiosis can be harnessed in horticultural ecosystems was performed. Modification of plant morphology, phosphorus availability and gene transcription involved with terpenoid biosynthetic pathways were identified as key mechanisms associated with terpenoid accumulation in AMF-colonised plants. In order to exploit AMF-plant symbioses in horticultural ecosystems it is important to consider the specificity of the AMF-plant association, the predominant factor affecting terpenoid accumulation, as well as the end use application of the harvested plant material. Future research should focus on resolving the relationship between ecologically matched AMF genotypes and terpenoid accumulation in plants to establish if these associations are effective in promoting mechanisms favourable for plant terpenoid accumulation.

Increased pulsatility, process irregularity, and nocturnal trough concentrations of growth hormone in amenorrheic compared to eumenorrheic athletes.

Amenorrheic athletes exhibit a spectrum of neuroendocrine disturbances, including alterations in the GH-insulin-like growth factor I (IGF-I) axis. Whether these changes are due to exercise or amenorrhea is incompletely characterized. The present study investigates spontaneous (overnight) and exercise-stimulated GH secretion and associated IGF-binding proteins (IGFBPs) in amenorrheic (AA; n = 5), and eumenorrheic athletes ( n = 5) matched for age, percent body fat (dual energy x-ray absorptiometry), training history, and maximal oxygen consumption. Each volunteer participated in two hospital admissions consisting of a 50-min submaximal exercise bout (70% maximal oxygen consumption) and an 8-h nocturnal sampling period. Deconvolution analysis of serum GH concentration time series revealed increases in the half-life of GH (60%) and the number of secretory bursts (85%) as well as a decrease in their half-duration (50%) and the mass of GH secreted per pulse (300%) in the AA cohort. Time occupancy at elevated trough GH concentrations was significantly increased, and GH pulsatility (approximate entropy) was more irregular in the AA group. During exercise, AA exhibited a reversal of the normal relationship between IGF-I and GH, and a 4- to 5-fold blunting of stimulated peak and integrated GH secretion. Fasting levels of plasma IGF-I, IGFBP-3, and IGFBP-1 appeared to be unaffected by menstrual status. In ensemble, this phenotype of GH release in amenorrheic athletes suggests disrupted neuroregulation of episodic GH secretion, possibly reflecting decreased somatostinergic inhibition basally, and reduced GHRH output in response to exercise compared with eumenorrheic athletes. Accordingly, we postulate that the amenorrheic state, beyond the exercise experience per se, alters the neuroendocrine control of GH output in amenorrheic athletes.

Prolonged efficacy of short acting insulin Lispro in combination with human ultralente in insulin-dependent diabetes mellitus.

Insulin Lispro is a newly FDA approved analog of human insulin that exhibits rapid absorption and a short duration of action after sc injection. Although Lispro insulin improves immediate postprandial glycemia compared to Regular insulin, long term trials of Lispro insulin have not shown improvement in overall glycemic control, as determined by glycosylated hemoglobin. We hypothesize that this lack of improvement is attributable to the development of late postprandial hyperglycemia secondary to a waning of Lispro insulin's effect in conjunction with continued meal absorption. This study was designed to evaluate the duration of Lispro-induced reductions in plasma glucose after a standardized meal when Lispro insulin is incorporated into a regimen typically employed in insulin-dependent diabetes mellitus. After establishment of euglycemia overnight, 12 healthy IDDM patients received human Ultralente insulin (0.2 U/kg) alone and in combination with each of the following treatments in random sequence immediately before ingesting a 750-Cal American Diabetes Association breakfast: 1) 0.15 U/kg human Regular insulin (Regular 0.15 group), 2) 0.15 U/kg Lispro insulin (Lispro 0.15 group), 3) 0.1 U/kg Lispro insulin (Lispro 0.1 group), and 4) an equimolar (1:1) mixture of Lispro and Regular insulins (0.15 U/kg; 1:1 Mix group). Glucose and hormonal parameters were assessed for 8 h after the meal. Peak postprandial glucose was increased in the Regular insulin group compared to that in all groups that incorporated Lispro insulin (P < 0.001). Glucose area under the curve (AUC) was decreased in the Lispro 0.15 group compared to that in the Lispro 0.1 group, and glucose AUC was decreased in the Lispro 0.15 and 1:1 Mix groups compared to that in the group given Regular insulin (P < 0.001). Mean plasma glucose concentrations during the final hour of study were increased in the Ultralente group compared with those in all other treatment groups and were increased in the Lispro 0.1 group compared with those in the Regular, Lispro 0.15, and 1:1 Mix groups (P < 0.05). Insulin AUC was significantly reduced in the Lispro 0.1 group compared to those in all other short acting insulin groups (P < 0.001), and time to peak insulin was more rapid in the two Lispro groups than those in all other treatment groups (P < 0.01). The glucagon response was significantly greater in the Ultralente group compared to those with all other treatments. There was no difference in the development of hypoglycemia between the groups. This study demonstrates that the reductions in plasma glucose effected by Lispro insulin are consistent and stable for 8 h after meal ingestion when Lispro insulin is used in combination with human Ultralente insulin. These findings suggest that improvement in overall glycemia, as assessed by glycosylated hemoglobin, may be achievable with Lispro insulin if adequate doses are administered.

Nitrogen deposition in malnourished children with cystic fibrosis.

To determine the protein nutritional status of 21 malnourished children with cystic fibrosis (CF), total body nitrogen (TBN) was measured and the results were compared with 21 control subjects. CF patients demonstrated a lower TBN (P less than 0.001). When matched for height (n = 10) or bone age (n = 13), the CF patients still had a depressed TBN/height or TBN/lean body mass (P less than 0.05). To assess nitrogen deposition during nutritional rehabilitation, repeat TBN measurements were performed on the 21 CF patients. Nitrogen deposition ranged from -230 to 550 g/y and correlated with weight velocity (r = 0.78, P less than 0.001). Increased nitrogen deposition (greater than 150 g/y) was generally associated with normal height gain (height velocity SD score greater than -2.00) and weight gain (greater than 2.0 kg/y). Decreased nitrogen deposition was associated with poor weight gain but did not preclude normal linear growth. These data suggest an important role for TBN estimations in defining protein nutritional status in children and indicate that skeletal growth can continue in the presence of minimal nitrogen deposition.