RESUMO
BACKGROUND: It is unclear whether diet affects glycaemic control in type 2 diabetes (T2D), over and above its effects on bodyweight. We aimed to assess whether changes in dietary patterns altered glycaemic control independently of effects on bodyweight in newly diagnosed T2D. METHODS: We used data from 4-day food diaries, HbA1c and potential confounders in participants of the Early-ACTivity-In-Diabetes trial measured at 0, 6 and 12 months. At baseline, a 'carb/fat balance' dietary pattern and an 'obesogenic' dietary pattern were derived using reduced-rank regression, based on hypothesised nutrient-mediated mechanisms linking dietary intake to glycaemia directly or via obesity. Relationships between 0 and 6 month change in dietary pattern scores and baseline-adjusted HbA1c at 6 months (n = 242; primary outcome) were assessed using multivariable linear regression. Models were repeated for periods 6-12 months and 0-12 months (n = 194 and n = 214 respectively; secondary outcomes). RESULTS: Reductions over 0-6 months were observed in mean bodyweight (- 2.3 (95% CI: - 2.7, - 1.8) kg), body mass index (- 0.8 (- 0.9, - 0.6) kg/m2), energy intake (- 788 (- 953, - 624) kJ/day), and HbA1c (- 1.6 (- 2.6, -0.6) mmol/mol). Weight loss strongly associated with lower HbA1c at 0-6 months (ß = - 0.70 [95% CI - 0.95, - 0.45] mmol/mol/kg lost). Average fat and carbohydrate intakes changed to be more in-line with UK healthy eating guidelines between 0 and 6 months. Dietary patterns shifting carbohydrate intakes higher and fat intakes lower were characterised by greater consumption of fresh fruit, low-fat milk and boiled/baked potatoes and eating less of higher-fat processed meats, butter/animal fats and red meat. Increases in standardised 'carb/fat balance' dietary pattern score associated with improvements in HbA1c at 6 months independent of weight loss (ß = - 1.54 [- 2.96, - 0.13] mmol/mol/SD). No evidence of association with HbA1c was found for this dietary pattern at other time-periods. Decreases in 'obesogenic' dietary pattern score were associated with weight loss (ß = - 0.77 [- 1.31, - 0.23] kg/SD) but not independently with HbA1c during any period. CONCLUSIONS: Promoting weight loss should remain the primary nutritional strategy for improving glycaemic control in early T2D. However, improving dietary patterns to bring carbohydrate and fat intakes closer to UK guidelines may provide small, additional improvements in glycaemic control. TRIAL REGISTRATION: ISRCTN92162869 . Retrospectively registered on 25 July 2005.
Assuntos
Diabetes Mellitus Tipo 2 , Glicemia , Peso Corporal , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/análise , Controle Glicêmico , Humanos , Redução de PesoRESUMO
AIMS: Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes. METHODS: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). RESULTS: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. CONCLUSIONS: Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19-22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6-8 March 2019.
Assuntos
Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Ilhotas Pancreáticas/patologia , Adulto , Idade de Início , Autoanticorpos/imunologia , Índice de Massa Corporal , Peptídeo C/sangue , Diabetes Mellitus/classificação , Diabetes Mellitus/genética , Diabetes Mellitus/imunologia , Diabetes Mellitus/patologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Humanos , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Pâncreas/patologia , Reprodutibilidade dos Testes , Adulto Jovem , Transportador 8 de Zinco/imunologiaRESUMO
BACKGROUND: The diagnosis of hyperglycaemia in sub-Saharan Africa (SSA) is challenging. Blood glucose levels obtained during oral glucose tolerance test (OGTT) may not reflect home glycaemic profiles. We compare OGTT results with home glycaemic profiles obtained using the FreeStyle Libre continuous glucose monitoring device (FSL-CGM). METHODS: Twenty-eight women (20 with gestational diabetes [GDM], 8 controls) were recruited following OGTT between 24 and 28 weeks of gestation. All women wore the FSL-CGM device for 48-96 h at home in early third trimester, and recorded a meal diary. OGTT was repeated on the final day of FSL-CGM recording. OGTT results were compared with ambulatory glycaemic variables, and repeat OGTT was undertaken whilst wearing FSL-CGM to determine accuracy of the device. RESULTS: FSL-CGM results were available for 27/28 women with mean data capture 92.8%. There were significant differences in the ambulatory fasting, post-prandial peaks, and mean glucose between controls in whom both primary and secondary OGTT was normal (n = 6) and those with two abnormal OGTTs or "true" GDM (n = 7). There was no difference in ambulatory mean glucose between these controls and the 13 women who had an abnormal primary OGTT and normal repeat OGTT. These participants had significantly lower body mass index (BMI) than the true GDM group (29.0 Vs 36.3 kg/m2, p-value 0.014). Paired OGTT/FSL-CGM readings revealed a Mean Absolute difference (MAD) -0.58 mmol/L and Mean Absolute Relative Difference (MARD) -11.9%. Bland-Altman plot suggests FSL-CGM underestimated blood glucose by approximately 0.78 mmol/L. CONCLUSION: Diagnosis of GDM on a single OGTT identifies a proportion of women who do not have a significantly higher home glucose levels than controls. This raises questions about factors which may affect the reproducibility of OGTT in this population, including food insecurity and atypical phenotypes of diabetes. More investigation is needed to understand the suitability of the OGTT as a diagnostic test in sub-Saharan Africa.
Assuntos
Automonitorização da Glicemia/estatística & dados numéricos , Diabetes Gestacional/diagnóstico , Teste de Tolerância a Glucose/estatística & dados numéricos , Adulto , Glicemia/análise , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/normas , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Estudos de Viabilidade , Feminino , Teste de Tolerância a Glucose/normas , Humanos , Gravidez , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Uganda/epidemiologia , Adulto JovemRESUMO
AIMS: Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA1c , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA1c in those with long duration (> 5 years) Type 1 diabetes. METHODS: We conducted a cross-sectional case-control study of 221 people (median age 24 years) with Type 1 diabetes. We confirmed ongoing endogenous insulin secretion by measuring C-peptide after a mixed-meal tolerance test. We compared self-reported hypoglycaemia (n = 160), HbA1c , insulin dose and microvascular complications (n = 140) in those with preserved and low C-peptide. RESULTS: Stimulated median (IQR) C-peptide was 114 (43, 273) pmol/l and < 3 (< 3, < 3) pmol/l in those with preserved and low C-peptide respectively. Participants with preserved C-peptide had lower reported monthly rates of hypoglycaemia, with 21% fewer symptomatic episodes, 5.9 vs. 7.5 [incidence rate ratio (IRR) 0.79, P = 0.001], and 65% fewer asymptomatic episodes, 1.0 vs. 2.9 (IRR 0.35, P < 0.001). Those with preserved C-peptide had a lower insulin dose (0.68 vs. 0.81 units/kg, P = 0.01) but similar HbA1c (preserved 69 vs. low 67 mmol/mol, P = 0.06). CONCLUSIONS: Adults with Type 1 diabetes and preserved endogenous insulin production receiving usual care in the UK have lower daily insulin doses and fewer self-reported hypoglycaemic episodes, but no difference in HbA1c . This is consistent with non-intensive treatment in previous studies, and suggests a need to consider therapy intensification to gain full benefit of preserved endogenous insulin.
Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemia/sangue , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Glicemia/análise , Glicemia/metabolismo , Automonitorização da Glicemia , Peptídeo C/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Reino Unido/epidemiologia , Adulto JovemRESUMO
The origin and maintenance of mating preferences continues to be an important and controversial topic in sexual selection research. Leks and lek-like mating systems, where individuals gather in particular spots for the sole purpose of mate choice, are particularly puzzling, because the strong directional selection imposed by mate choice should erode genetic variation among competing individuals and negate any benefit for the choosing sex. Here, we take advantage of the lek-like mating system of the worm pipefish (Nerophis lumbriciformis) to test the phenotype-linked fertility hypothesis for the maintenance of mating preferences. We use microsatellite markers to perform a parentage analysis, along with a mark-recapture study, to confirm that the worm pipefish has an unusual mating system that strongly resembles a female lek, where females display and males visit the lek to choose mates. Our results show that the most highly ornamented females occupy positions near the centre of the breeding area, and males mating with these females receive fuller broods with larger eggs compared to males mating with less-ornamented females. We also conduct a laboratory experiment to show that female ornaments are condition-dependent and honestly signal reproductive potential. Overall, these results are consistent with the predictions of a sex-independent version of the phenotype-linked fertility hypothesis, as male preference for female ornaments correlates with fertility benefits.
Assuntos
Fertilidade , Preferência de Acasalamento Animal , Reprodução , Smegmamorpha/fisiologia , Animais , Feminino , Masculino , Fenótipo , Smegmamorpha/genéticaRESUMO
BACKGROUND: Measuring endogenous insulin secretion using C-peptide can assist diabetes management, but standard stimulation tests are impractical for clinical use. Random non-fasting C-peptide assessment would allow testing when a patient is seen in clinic. METHODS: We compared C-peptide at 90 min in the mixed meal tolerance test (sCP) with random non-fasting blood C-peptide (rCP) and random non-fasting urine C-peptide creatinine ratio (rUCPCR) in 41 participants with insulin-treated diabetes [median age 72 (interquartile range 68-78); diabetes duration 21 (14-31) years]. We assessed sensitivity and specificity for previously reported optimal mixed meal test thresholds for severe insulin deficiency (sCP < 200 pmol//l) and Type 1 diabetes/inability to withdraw insulin (< 600 pmol//l), and assessed the impact of concurrent glucose. RESULTS: rCP and sCP levels were similar (median 546 and 487 pmol//l, P = 0.92). rCP was highly correlated with sCP, r = 0.91, P < 0.0001, improving to r = 0.96 when excluding samples with concurrent glucose < 8 mmol//l. An rCP cut-off of 200 pmol//l gave 100% sensitivity and 93% specificity for detecting severe insulin deficiency, with area under the receiver operating characteristic curve of 0.99. rCP < 600 pmol//l gave 87% sensitivity and 83% specificity to detect sCP < 600 pmol//l. Specificity improved to 100% when excluding samples with concurrent glucose < 8 mmol//l. rUCPCR (0.52 nmol/mmol) was also well-correlated with sCP, r = 0.82, P < 0.0001. A rUCPCR cut-off of < 0.2 nmol/ mmol gave sensitivity and specificity of 83% and 93% to detect severe insulin deficiency, with area under the receiver operating characteristic curve of 0.98. CONCLUSIONS: Random non-fasting C-peptide measures are strongly correlated with mixed meal C-peptide, and have high sensitivity and specificity for identifying clinically relevant thresholds. These tests allow assessment of C-peptide at the point patients are seen for clinical care.
Assuntos
Peptídeo C/sangue , Técnicas de Laboratório Clínico/métodos , Diabetes Mellitus Tipo 1/diagnóstico , Técnicas de Diagnóstico Endócrino , Insulina/metabolismo , Idoso , Diabetes Mellitus Tipo 1/sangue , Jejum/sangue , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Secreção de Insulina , Masculino , RefeiçõesRESUMO
Microsatellite parentage analysis was applied to 22 broods of the northern pipefish Syngnathus fuscus for the first time. The majority of males mated singly, 23% of males mated with two females, and no males mated with more than two females. The arrangement of embryos within the brood pouch of multiply mated males reflects a previously undocumented fill pattern where full-sib groups are segregated within the pouch by both right and left sides as well as anterior and posterior ends.
Assuntos
Reprodução/fisiologia , Smegmamorpha/fisiologia , Viviparidade não Mamífera/fisiologia , Animais , Feminino , Masculino , Repetições de Microssatélites , Smegmamorpha/genéticaRESUMO
Understanding how selection acts on traits individually and in combination is an important step in deciphering the mechanisms driving evolutionary change, but for most species, and especially those in which sexual selection acts more strongly on females than on males, we have no estimates of selection coefficients pertaining to the multivariate sexually selected phenotype. Here, we use a laboratory-based mesocosm experiment to quantify pre- and post-mating selection on female secondary sexual traits in the Gulf pipefish (Syngnathus scovelli), a sexually dimorphic, sex-role-reversed species in which ornamented females compete for access to choosy males. We calculate selection differentials and gradients on female traits, including ornament area, ornament number and body size for three episodes of selection related to female reproductive success (number of mates, number of eggs transferred and number of surviving embryos). Selection is strong on both ornament area and ornament size, and the majority of selection occurs during the premating episode of selection. Interestingly, selection on female body size, which has been detected in previous studies of Gulf pipefish, appears to be indirect, as evidenced by a multivariate analysis of selection gradients. Our results show that sexual selection favours either many bands or larger bands in female Gulf pipefish.
Assuntos
Peixes/genética , Peixes/fisiologia , Preferência de Acasalamento Animal , Animais , Evolução Molecular , Feminino , Peixes/anatomia & histologia , Aptidão Genética , Masculino , Repetições de Microssatélites , Modelos Biológicos , Fenótipo , Seleção Genética , Caracteres SexuaisRESUMO
C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes. Measurement of insulin secretion using C-peptide can be helpful in clinical practice: differences in insulin secretion are fundamental to the different treatment requirements of Type 1 and Type 2 diabetes. This article reviews the use of C-peptide measurement in the clinical management of patients with diabetes, including the interpretation and choice of C-peptide test and its use to assist diabetes classification and choice of treatment. We provide recommendations for where C-peptide should be used, choice of test and interpretation of results. With the rising incidence of Type 2 diabetes in younger patients, the discovery of monogenic diabetes and development of new therapies aimed at preserving insulin secretion, the direct measurement of insulin secretion may be increasingly important. Advances in assays have made C-peptide measurement both more reliable and inexpensive. In addition, recent work has demonstrated that C-peptide is more stable in blood than previously suggested or can be reliably measured on a spot urine sample (urine C-peptide:creatinine ratio), facilitating measurement in routine clinical practice. The key current clinical role of C-peptide is to assist classification and management of insulin-treated patients. Utility is greatest after 3-5 years from diagnosis when persistence of substantial insulin secretion suggests Type 2 or monogenic diabetes. Absent C-peptide at any time confirms absolute insulin requirement and the appropriateness of Type 1 diabetes management strategies regardless of apparent aetiology.
Assuntos
Peptídeo C/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Insulina/metabolismo , Peptídeo C/sangue , Peptídeo C/urina , Diabetes Mellitus/classificação , Humanos , Resistência à Insulina , Secreção de Insulina , PrognósticoRESUMO
AIMS: To determine the prevalence and clinical characteristics of absolute insulin deficiency in long-standing Type 2 diabetes, using a strategy based on home urinary C-peptide creatinine ratio measurement. METHODS: We assessed the urinary C-peptide creatinine ratios, from urine samples taken at home 2 h after the largest meal of the day, in 191 insulin-treated subjects with Type 2 diabetes (diagnosis age ≥45 years, no insulin in the first year). If the initial urinary C-peptide creatinine ratio was ≤0.2 nmol/mmol (representing absolute insulin deficiency), the assessment was repeated. A standardized mixed-meal tolerance test with 90-min stimulated serum C-peptide measurement was performed in nine subjects with a urinary C-peptide creatinine ratio ≤ 0.2 nmol/mmol (and in nine controls with a urinary C-peptide creatinine ratio >0.2 nmol/mmol) to confirm absolute insulin deficiency. RESULTS: A total of 2.7% of participants had absolute insulin deficiency confirmed by a mixed-meal tolerance test. They were identified initially using urinary C-peptide creatinine ratio: 11/191 subjects (5.8%) had two consistent urinary C-peptide creatinine ratios ≤ 0.2 nmol/mmol; 9 of these 11 subjects completed a mixed-meal tolerance test and had a median stimulated serum C-peptide of 0.18 nmol/l. Five of these 9 had stimulated serum C-peptide <0.2 nmol/l and 9/9 subjects with urinary C-peptide creatinine ratio >0.2 had endogenous insulin secretion confirmed by the mixed-meal tolerance test. Compared with subjects with a urinary C-peptide creatinine ratio >0.2 nmol/mmol, those with confirmed absolute insulin deficiency had a shorter time to insulin treatment (median 2.5 vs. 6 years, P=0.005) and lower BMI (25.1 vs. 29.1 kg/m(2) , P=0.04). Two out of the five patients with absolute insulin deficiency were glutamic acid decarboxylase autoantibody-positive. CONCLUSIONS: Absolute insulin deficiency may occur in long-standing Type 2 diabetes, and cannot be reliably predicted by clinical features or autoantibodies. Absolute insulin deficiency in Type 2 diabetes may increase the risk of hypoglycaemia and ketoacidosis, as in Type 1 diabetes. Its recognition should help guide treatment, education and management. The urinary C-peptide creatinine ratio is a practical non-invasive method to aid detection of absolute insulin deficiency, with a urinary C-peptide creatinine ratio > 0.2 nmol/mmol being a reliable indicator of retained endogenous insulin secretion.
Assuntos
Peptídeo C/biossíntese , Peptídeo C/urina , Creatinina/urina , Diabetes Mellitus Tipo 2/urina , Insulina/deficiência , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: The mixed meal tolerance test is the gold standard measure of endogenous insulin secretion. Practical issues limit the routine clinical use of this test, including omitting insulin prior to the ingestion of a high-carbohydrate liquid mixed meal, which can result in marked hyperglycaemia. We aimed to assess whether insulin omission is necessary during the mixed meal tolerance test and whether fasting C-peptide was a practical alternative to the test. METHODS: Ninety-one adults with insulin-treated diabetes (Type 1 n = 56, Type 2 n = 35) underwent two mixed meal tolerance tests; one standard without insulin and one with the patient's usual morning insulin. RESULTS: The 90-min serum C-peptide was highly correlated in the standard mixed meal tolerance test and the test with insulin (r = 0.98, P < 0.0001). There was a 20% reduction in the peak C-peptide value when insulin was given {test with insulin [0.39 (0.01-1.16) vs. test without insulin 0.48 (0.01-1.36) nmol/l, P = 0.001]}, but the original serum C-peptide cut-off for significant endogenous insulin secretion (≥ 0.2 nmol/l) still correctly classified 90/91 patients (98% sensitivity/100% specificity). Fasting serum C-peptide was highly correlated to 90-min serum C-peptide during the test (r = 0.97, P < 0.0001). A fasting serum C-peptide ≥ 0.07 nmol/l was the optimal cut-off (100% sensitivity and 97% specificity) for significant endogenous insulin secretion (defined as 90-min stimulated serum C-peptide ≥ 0.2 nmol/l). CONCLUSIONS: Insulin omission may not always be necessary during a mixed meal tolerance test and fasting serum C-peptide may offer a practical alternative in insulin-treated patients.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Teste de Tolerância a Glucose/métodos , Hiperglicemia/sangue , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina/sangue , Refeições , Adolescente , Adulto , Idade de Início , Glicemia/metabolismo , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inglaterra , Jejum/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/sangue , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Evolutionary biologists have developed several indices, such as selection gradients (ß) and the opportunity for sexual selection (I(s) ), to quantify the actual and/or potential strength of sexual selection acting in natural or experimental populations. In a recent paper, Klug et al. (J. Evol. Biol.23, 2010, 447) contend that selection gradients are the only legitimate metric for quantifying sexual selection. They argue that I(s) and similar mating-system-based metrics provide unpredictable results, which may be uncorrelated with selection acting on a trait, and should therefore be abandoned. We find this view short-sighted and argue that the choice of metric should be governed by the research question at hand. We describe insights that measures such as the opportunity for selection can provide and also argue that Klug et al. have overstated the problems with this approach while glossing over similar issues with the interpretation of selection gradients. While no metric perfectly characterizes sexual selection in all circumstances, thoughtful application of existing measures has been and continues to be informative in evolutionary studies.
Assuntos
Genética Populacional/métodos , Seleção Genética , Caracteres Sexuais , Animais , Feminino , Masculino , Razão de MasculinidadeRESUMO
AIMS: Serum C-peptide measurement can assist clinical management of diabetes, but practicalities of collection limit widespread use. Urine C-peptide creatinine ratio may be a non-invasive practical alternative. The stability of C-peptide in urine allows outpatient or community testing. We aimed to assess how urine C-peptide creatinine ratio compared with serum C-peptide measurement during a mixed-meal tolerance test in individuals with late-onset, insulin-treated diabetes. METHODS: We correlated the gold standard of a stimulated serum C-peptide in a mixed-meal tolerance test with fasting and stimulated (mixed-meal tolerance test, standard home meal and largest home meal) urine C-peptide creatinine ratio in 51 subjects with insulin-treated diabetes (diagnosis after age 30 years, median age 66 years, median age at diagnosis 54, 42 with Type 2 diabetes, estimated glomerular filtration rate > 60 ml min(-1) 1.73 m(-2) ). RESULTS: Ninety-minute mixed-meal tolerance test serum C-peptide is correlated with mixed-meal tolerance test-stimulated urine C-peptide creatinine ratio (r = 0.82), urine C-peptide creatinine ratio after a standard breakfast at home (r = 0.73) and urine C-peptide creatinine ratio after largest home meal (r = 0.71). A stimulated (largest home meal) urine C-peptide creatinine ratio cut-off of 0.3 nmol/mmol had a 100% sensitivity and 96% specificity (area under receiver operating characteristic curve = 0.99) in identifying subjects without clinically significant endogenous insulin secretion (mixed-meal tolerance test-stimulated C-peptide < 0.2 nmol/l). In detecting a proposed serum C-peptide threshold for insulin requirement (stimulated serum C-peptide < 0.6 nmol/l), a stimulated (largest home meal) urine C-peptide creatinine ratio cut-off of 0.6 nmol/mmol had a sensitivity and specificity of 92%. CONCLUSION: In patients with insulin-treated diabetes diagnosed after age 30 years, urine C-peptide creatinine ratio is well correlated with serum C-peptide and may provide a practical alternative measure to detect insulin deficiency for use in routine clinical practice.
Assuntos
Peptídeo C/urina , Creatinina/urina , Diabetes Mellitus Tipo 1/urina , Diabetes Mellitus Tipo 2/urina , Glucagon/urina , Hemoglobinas Glicadas/urina , Idade de Início , Idoso , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Jejum , Feminino , Glucagon/sangue , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
The Cenozoic collision between the Indian and Asian continents formed the Tibetan plateau, beginning about 70 million years ago. Since this time, at least 1,400 km of convergence has been accommodated by a combination of underthrusting of Indian and Asian lithosphere, crustal shortening, horizontal extrusion and lithospheric delamination. Rocks exposed in the Himalaya show evidence of crustal melting and are thought to have been exhumed by rapid erosion and climatically forced crustal flow. Magnetotelluric data can be used to image subsurface electrical resistivity, a parameter sensitive to the presence of interconnected fluids in the host rock matrix, even at low volume fractions. Here we present magnetotelluric data from the Tibetan-Himalayan orogen from 77 degrees E to 92 degrees E, which show that low resistivity, interpreted as a partially molten layer, is present along at least 1,000 km of the southern margin of the Tibetan plateau. The inferred low viscosity of this layer is consistent with the development of climatically forced crustal flow in Southern Tibet.
RESUMO
The reaction of the Tc(II) nitrosyl complex (Bu(4)N)[Tc(NO)Cl(4)] with Di-(2-picolyl)(NEt)amine in methanol yields the neutral complex [Tc(NO)Cl(py-N(Et)-py)]. The reaction of the Tc(I) nitrosyl complex [Tc(NO)Cl(2)(HOMe)(PPh(3))(2)] with this tridentate ligand yields cationic [Tc(NO)Cl(py-N(Et)-py)(PPh(3))]Cl. These two complexes have been structurally characterized. The reaction of [Tc(NO)Cl(2)(HOMe)(PPh(3))(2)] with the tetradentate ligand 1,4-Bis(2-pyridylmethyl)-1,4-diazobutane yields a mixture of products including cationic [Tc(NO)Cl(py-NH-NH-py)]Cl and cationic [Tc(NO)Cl(PPh(3))(py-NH-NH~py)]Cl, with a pyridyl terminus left dangling.
RESUMO
The goal of this review was to provide a historical overview of how molecular techniques have increased the understanding of the ecology and evolution of the family Syngnathidae (pipefishes, seahorses and seadragons). Molecular studies based primarily on mitochondrial DNA markers have proved their worth by elucidating complex phylogenetic relationships within the family. Phylogeographic studies, which have revealed how life-history traits and past climatic events shape geographic distributions and patterns of genetic variation within syngnathid species, also provide interesting case studies for the conservation and management of threatened species. The application of microsatellite DNA markers has opened a floodgate of studies concerned with the breeding biology of these fishes, which are interesting due to their unique reproductive mode of male pregnancy. Research in this area has contributed significantly to the understanding of mating patterns and sexual selection. Molecular markers may also be employed in studies of demography, migration and local breeding population sizes. Genomic studies have identified genes that are probably involved in male pregnancy and promise additional insights into various aspects of syngnathid biology at the level of the gene. Despite these advances, much more remains to be explored. Goals for future research should include: (1) a more inclusive phylogeny to resolve outstanding issues concerning the relationships within the family and higher order taxa, (2) a broader use of molecular studies to aid management and conservation efforts, (3) the inclusion of more genera in comparative behavioural studies and (4) the continued development of genomic resources for syngnathids to facilitate comparative genomic work.
Assuntos
Smegmamorpha/genética , Animais , Conservação dos Recursos Naturais , Genômica , Preferência de Acasalamento Animal , Filogenia , Filogeografia , Dinâmica PopulacionalRESUMO
In two experiments, radioactively labelled nutrients (either (3)H-labelled amino-acid mixture or (14)C-labelled glucose) were tube-fed to brooding male Syngnathus typhle. Both nutrients were taken up by the males and radioactivity generally increased in the brood pouch tissue with time. Furthermore, a low but significant increase of (3)H-labelled amino acids in embryos was found over the experimental interval (48 h), whereas in the (14)C-glucose experiment the radioactivity was taken up by the embryos but did not increase over the experimental time (320 min). Uptake of radioisotopes per embryo did not differ with embryo size. A higher uptake mg(-1) tissue of both (3)H-labelled amino acids and (14)C-labelled glucose was found in smaller embryos, possibly due to a higher relative metabolic rate or to a higher surface-area-to-volume ratio compared to larger embryos. Uptake in embryos was not influenced by male size, embryonic developmental advancement or position in the brood pouch. It is concluded that brooding males provide amino acids, and probably also glucose, to the developing embryos in the brood pouch.
Assuntos
Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário , Reprodução , Smegmamorpha/fisiologia , Aminoácidos/metabolismo , Animais , Tamanho Corporal , Radioisótopos de Carbono , Glucose/metabolismo , Masculino , TrítioRESUMO
With the growing demand for animal-sourced foods and a serious concern over climate impacts associated with livestock farming, the sheep industry worldwide faces the formidable challenge of increasing the overall product supply while improving its resource use efficiency. As an evidence base for research to identify key drivers behind animal growth and carcass quality, longitudinal matched data of 741 ewes and 2978 lambs were collected at the North Wyke Farm Platform, a farm-scale grazing trial in Devon, UK, between 2011 and 2019. A subset of these data was subsequently analysed in a study to assess the feasibility of using a lamb's early-life liveweight as a predictor of carcass quality [1]. The data also have the potential to offer insight into key performance indicators (KPIs) for the sheep industry, or what variables farmers should measure and target to increase profitability.
RESUMO
The commercial value of lamb carcasses is primarily determined by their weight and quality, with the latter commonly quantified according to muscle coverage and fat depth. The ability to predict these quality scores early in the season could be of substantial value to sheep producers, as this would enable tailored flock management strategies for different groups of animals. Existing methods of carcass quality prediction, however, require either expensive equipment or information immediately before slaughter, leaving them unsuitable as a decision support tool for small to medium-scale enterprises. Using seven-year high-resolution data from the North Wyke Farm Platform, a system-scale grazing trial in Devon, UK, this paper investigates the feasibility of using a lamb's early-life liveweight to predict the carcass quality realised when the animal reaches the target weight. The results of multinomial regression models showed that lambs which were heavier at weaning, at 13â¯weeks of age, were significantly more likely to have leaner and more muscular carcasses. An economic analysis confirmed that these animals produced significantly more valuable carcasses at slaughter, even after accounting for seasonal variation in lamb price that often favours early finishers. As the majority of heavier-weaned lambs leave the flock before lighter-weaned lambs, an increase in the average weaning weight could also lead to greater pasture availability for ewes in the latter stage of the current season, and thus an enhanced ewe condition and fertility for the next season. All information combined, therefore, a stronger focus on ewes' nutrition before and during lactation was identified as a key to increase system-wide profitability.