Early-life factors are associated with nocturnal cortisol and glucose effectiveness in Afro-Caribbean young adults.

CONTEXT: Early-life factors (including intrauterine growth retardation) may influence the development of type 2 diabetes. We postulated that birth size is associated with cortisol levels, which itself could alter serum adipomyokines (i.e. adiponectin, IGF-I, myostatin) and glucose metabolism. DESIGN: An observational study with 60 Afro-Caribbean young adults from a birth cohort. MEASUREMENTS: Fasting blood was drawn for serum adiponectin, IGF-I and myostatin. A frequently sampled intravenous glucose tolerance test measured insulin sensitivity (SI), acute insulin response (AIRg), disposition index (DI) and glucose effectiveness (Sg). Body composition was assessed by dual-energy X-ray absorptiometry. Salivary cortisol was collected at home at 0800 and 2300 h. Sex-adjusted correlations were used to explore the relationships between birth size, cortisol and the metabolic variables. RESULTS: The participants were 55% male, mean age 23·1 ± 0·5 years. Birth weight correlated positively with 2300-h cortisol (P = 0·04), although not after adjusting for gestational age. Gestational age was correlated with 2300 h cortisol (r = 0·38, P = 0·03), even after adjusting for birth weight (P = 0·02). 2300 h cortisol was not associated with adiponectin, IGF-I, myostatin, SI, AIRg or DI, but was negatively correlated with Sg (r = -0·30, P = 0·05) even after adjusting for birth and adult anthropometry. Adiponectin, IGF-I and myostatin were unrelated to glucose metabolism. CONCLUSIONS: Gestational age is associated with higher nocturnal cortisol, which in turn is associated with lower glucose effectiveness in adulthood. Higher glucose effectiveness could therefore be a compensatory mechanism to improve glucose uptake.

Faster rehabilitation weight gain during childhood is associated with risk of non-communicable disease in adult survivors of severe acute malnutrition.

Nutritional rehabilitation during severe acute malnutrition (SAM) aims to quickly restore body size and minimize poor short-term outcomes. We hypothesized that faster weight gain during treatment is associated with greater cardiometabolic risk in adult life. Anthropometry, body composition (DEXA), blood pressure, blood glucose, insulin and lipids were measured in a cohort of adults who were hospitalized as children for SAM between 1963 and 1993. Weight and height measured during hospitalization and at one year post-recovery were abstracted from hospital records. Childhood weight gain during nutritional rehabilitation and weight and height gain one year post-recovery were analysed as continuous variables, quintiles and latent classes in age, sex and minimum weight-for-age z-scores-adjusted regression models against adult measurements. Data for 278 adult SAM survivors who had childhood admission records were analysed. Of these adults, 85 also had data collected 1 year post-hospitalisation. Sixty percent of participants were male, mean (SD) age was 28.2 (7.7) years, mean (SD) BMI was 23.6 (5.2) kg/m2. Mean admission age for SAM was 10.9 months (range 0.3-36.3 months), 77% were wasted (weight-for-height z-scores<-2). Mean rehabilitation weight gain (SD) was 10.1 (3.8) g/kg/day and 61.6 (25.3) g/day. Rehabilitation weight gain > 12.9 g/kg/day was associated with higher adult BMI (difference = 0.5 kg/m2, 95% CI: 0.1-0.9, p = 0.02), waist circumference (difference = 1.4 cm, 95% CI: 0.4-2.4, p = 0.005), fat mass (difference = 1.1 kg, 95% CI: 0.2-2, p = 0.02), fat mass index (difference = 0.32kg/m2, 95% CI: -0.0001-0.6, p = 0.05), and android fat mass (difference = 0.09 kg, 95% CI: 0.01-0.2, p = 0.03). Post-recovery weight gain (g/kg/month) was associated with lean mass (difference = 1.3 kg, 95% CI: 0.3-2.4, p = 0.015) and inversely associated with android-gynoid fat ratio (difference = -0.03, 95% CI: -0.07to-0.001 p = 0.045). Rehabilitation weight gain exceeding 13g/kg/day was associated with adult adiposity in young, normal-weight adult SAM survivors. This challenges existing guidelines for treating malnutrition and warrants further studies aiming at optimising these targets.

Liver fat in adult survivors of severe acute malnutrition.

The association between severe acute malnutrition (SAM) in early childhood and liver fat in adults is unknown. We hypothesized that exposure to SAM, especially severe wasting, is associated with fatty liver later in life. In this observational study, abdominal CT was used to quantify mean liver attenuation (MLA) and liver:spleen attenuation ratio (L/S). Birth weight (BW), serum lipids, insulin resistance (homeostatic model assessment), anthropometry and intrabdominal fat were collected. Mean differences between diagnostic groups were tested and hierarchical regression analysis determined the best predictors of liver fat. We studied 88 adult SAM survivors and 84 community participants (CPs); age 29.0 ± 8.4 years, BMI 23.5 ± 5.0 kg/m2 (mean ± SDs). SAM survivors had less liver fat than CPs (using L/S) (p = 0.025). Severe wasting survivors (SWs) had lower BW (-0.51 kg; p = 0.02), were younger, thinner and had smaller waist circumference than oedematous malnutrition survivors (OMs). In the final regression model adjusting for age, sex, birth weight and SAM phenotype (i.e., oedematous malnutrition or severe wasting), SWs had more liver fat than OMs (using MLA) (B = 2.6 ± 1.3; p = 0.04) but similar liver fat using L/S (p = 0.07) and lower BW infants had less liver fat (MLA) (B = -1.8 ± 0.8; p = 0.03). Greater liver fat in SWs than OMs, despite having less body fat, supports our hypothesis of greater cardiometabolic risk in SWs. Other postnatal factors might influence greater liver fat in survivors of severe wasting, suggesting the need to monitor infants exposed to SAM beyond the acute episode.

The effect of wasting and stunting during severe acute malnutrition in infancy on insulin sensitivity and insulin clearance in adult life.

Adults who had non-edematous severe acute malnutrition (SAM) during infancy (i.e., marasmus) have worse glucose tolerance and beta-cell function than survivors of edematous SAM (i.e., kwashiorkor). We hypothesized that wasting and/or stunting in SAM is associated with lower glucose disposal rate (M) and insulin clearance (MCR) in adulthood.We recruited 40 nondiabetic adult SAM survivors (20 marasmus survivors (MS) and 20 kwashiorkor survivors (KS)) and 13 matched community controls. We performed 150-minute hyperinsulinaemic, euglycaemic clamps to estimate M and MCR. We also measured serum adiponectin, anthropometry, and body composition. Data on wasting (weight-for-height) and stunting (height-for-age) were abstracted from the hospital records.Children with marasmus had lower weight-for-height z-scores (WHZ) (-3.8 ± 0.9 vs. -2.2 ± 1.4; P < 0.001) and lower height-for-age z-scores (HAZ) (-4.6 ± 1.1 vs. -3.4 ± 1.5; P = 0.0092) than those with kwashiorkor. As adults, mean age (SD) of participants was 27.2 (8.1) years; BMI was 23.6 (5.0) kg/m2. SAM survivors and controls had similar body composition. MS and KS and controls had similar M (9.1 ± 3.2; 8.7 ± 4.6; 6.9 ± 2.5 mg.kg-1.min-1 respectively; P = 0.3) and MCR. WHZ and HAZ were not associated with M, MCR or adiponectin even after adjusting for body composition.Wasting and stunting during infancy are not associated with insulin sensitivity and insulin clearance in lean, young, adult survivors of SAM. These data are consistent with the finding that glucose intolerance in malnutrition survivors is mostly due to beta-cell dysfunction.

Developmental origins of cardiovascular risk in Jamaican children: the Vulnerable Windows Cohort study.

Both intra-uterine and early childhood development contribute to the risk of developing CVD in adult life. We therefore evaluated the maternal, placental, fetal, birth, infant and childhood determinants of cardiovascular risk in a cohort of Afro-Jamaican children. The Vulnerable Windows Cohort is a longitudinal survey of 569 mothers and their offspring recruited from the first trimester. The offspring's anthropometry was measured at birth, at 6 weeks, every 3 months to 1 year and then every 6 months. At mean age 11.5 years, fasting blood was sampled for glucose, insulin and lipids. Analyses were confined to 296 women and their offspring who had complete data. Waist circumference (WC) was related to maternal weight and BMI, placental weight and to the size of the offspring in utero, at birth and the rate of growth in childhood (P < 0.05). Total cholesterol, TAG and glucose concentrations were unrelated to maternal, placental, fetal, neonatal and childhood measurements. Fasting insulin and homeostasis model assessment of insulin resistance were related to maternal weight and BMI (P < 0.05), but not after adjusting for WC. HDL-cholesterol was inversely related to placental and birth weight, and inversely related to weight and BMI throughout childhood (P < 0.001), but not after adjusting for WC. Systolic blood pressure was directly related to maternal weight, child's height, weight and BMI (P < 0.05), but not after adjustment for WC. Systolic blood pressure and fasting glucose concentration were inversely related to birth weight in boys but directly associated in girls. We concluded that maternal anthropometry during pregnancy, fetal size, and childhood growth rate contribute to cardiovascular risk factors in childhood.

Childhood severe acute malnutrition is associated with metabolic changes in adulthood.

BACKGROUNDSevere acute malnutrition (SAM) is a major contributor to global mortality in children under 5 years. Mortality has decreased; however, the long-term cardiometabolic consequences of SAM and its subtypes, severe wasting (SW) and edematous malnutrition (EM), are not well understood. We evaluated the metabolic profiles of adult SAM survivors using targeted metabolomic analyses.METHODSThis cohort study of 122 adult SAM survivors (SW = 69, EM = 53) and 90 age-, sex-, and BMI-matched community participants (CPs) quantified serum metabolites using direct flow injection mass spectrometry combined with reverse-phase liquid chromatography. Univariate and sparse partial least square discriminant analyses (sPLS-DAs) assessed differences in metabolic profiles and identified the most discriminative metabolites.RESULTSSeventy-seven metabolite variables were significant in distinguishing between SAM survivors (28.4 ± 8.8 years, 24.0 ± 6.1 kg/m2) and CPs (28.4 ± 8.9 years, 23.3 ± 4.4 kg/m2) (mean ± SDs) in univariate and sPLS-DA models. Compared with CPs, SAM survivors had less liver fat; higher branched-chain amino acids (BCAAs), urea cycle metabolites, and kynurenine/tryptophan (KT) ratio (P < 0.001); and lower ß-hydroxybutyric acid and acylcarnitine/free carnitine ratio (P < 0.001), which were both associated with hepatic steatosis (P < 0.001). SW and EM survivors had similar metabolic profiles as did stunted and nonstunted SAM survivors.CONCLUSIONAdult SAM survivors have distinct metabolic profiles that suggest reduced ß-oxidation and greater risk of type 2 diabetes (BCAAs, KT ratio, urea cycle metabolites) compared with CPs. This indicates that early childhood SAM exposure has long-term metabolic consequences that may worsen with age and require targeted clinical management.FUNDINGHealth Research Council of New Zealand, Caribbean Public Health Agency, Centre for Global Child Health at the Hospital for Sick Children. DST is an Academic Fellow and a Restracomp Fellow at the Centre for Global Child Health. GBG is a postdoctoral fellow of the Research Foundation Flanders.

Impact of adiponectin and ghrelin on incident glucose intolerance and on weight change.

OBJECTIVES: Adiponectin and ghrelin are associated with adiposity and type 2 diabetes in several studies. We sought to prospectively determine the interaction of adiponectin and ghrelin in the development of adiposity and hyperglycaemia. DESIGN: Prospective observational study. PARTICIPANTS: 393 community-dwelling Afro-Jamaicans (mean age 47 +/- 13 years; BMI 27.3 +/- 6.3 kg/m(2); 63% women) without glucose intolerance at baseline. MEASUREMENTS: Anthropometry, fasting plasma glucose, 2-h plasma glucose, insulin resistance (HOMA-IR), adiponectin and ghrelin concentrations were measured at baseline and 4.1 +/- 0.9 years later. Multivariate analyses were used to explore the associations of HOMA-IR, adiponectin and ghrelin with weight change and glycaemia. Results The mean weight change was 2.6 +/- 5.5 kg. There were 114 incident cases of impaired glucose tolerance (IGT) and 35 cases of diabetes mellitus. Adiponectin was positively correlated with age and female sex (P-values < 0.01). After adjusting for age and sex, adiponectin and ghrelin were significantly correlated with weight at baseline and follow-up. However, they were not associated with weight change even after further adjustment for baseline weight. Adiponectin, but not ghrelin, was associated with 2-h glucose concentrations at follow-up even after adjusting for age, sex, HOMA-IR and BMI (P = 0.04). In the fully adjusted logistic regression model, adiponectin predicted incident IGT (OR 0.93; 95% CI: 0.87-0.99) and attenuated the effect of BMI on incident IGT. CONCLUSIONS: These longitudinal data show that adiponectin and ghrelin may not be causally involved in the development of obesity. However, adiponectin is independently associated with decreased risk of incident IGT.

Nonalcoholic Fatty Liver Disease in Nonobese Subjects of African Origin Has Atypical Metabolic Characteristics.

BACKGROUND: Nonobese nonalcoholic fatty liver disease is reported in several populations. However, because persons of African origin display unique fat accumulation, insulin resistance, and lipid profiles, we investigated fatty liver in nonobese persons of African origin. METHOD: We recruited 78 urban Jamaican volunteers. CT was used to estimate liver and abdominal fat and dual-energy X-ray absorptiometry to measure body composition. Fasting blood was collected for lipids, alanine aminotransferase (ALT), adiponectin, and fetuin-A. Homeostatic model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), insulinogenic index (IGI), and oral disposition index (oDI) were calculated after a 75-g oral glucose tolerance test. RESULTS: Fifty-two percent of participants were male; mean (±SD) age was 28.5 ± 7.8 years, and body mass index was 22.4 ± 3.0 kg/m2. Mean liver attenuation (MLA) and liver/spleen (LS) ratio, both inversely correlated to liver fat, were 62.8 ± 4.3 HU and 1.2 ± 0.1, respectively; 3.8% of participants had liver fat >30% (LS ratio < 1). In age, sex, and BMI-adjusted correlations, MLA was negatively associated with weight (r = -0.30; P = 0.009) and height (r = -0.28; P = 0.017) and was associated with fasting glucose (r = 0.23; P = 0.05), fasting insulin (r = 0.42; P ≤ 0.001) and HOMA-IR (r = 0.35; P = 0.004). Serum lipids, ALT, adiponectin, fetuin-A, WBISI, IGI, and oDI were not associated with liver fat. CONCLUSIONS: In nonobese Afro-Caribbean participants, greater liver fat was associated with weight and height and lower fasting insulin and hyperinsulinemia appears to be influential in the reduction of NAFLD. These findings may be influenced by ethnicity, body size, and method of estimating liver fat.

Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia.

AIMS/HYPOTHESES: We hypothesized that there is decreased synthesis of glutathione (GSH) in type 2 diabetes (T2DM) especially in the presence of microvascular complications, and this is dependent on the degree of hyperglycemia. METHODS: In this case-control study, we recruited 16 patients with T2DM (7 without and 9 with microvascular complications), and 8 age- and sex-matched non-diabetic controls. We measured GSH synthesis rate using an infusion of [2H2]-glycine as isotopic tracer and collection of blood samples for liquid chromatography mass spectrometric analysis. RESULTS: Compared to the controls, T2DM patients had lower erythrocyte GSH concentrations (0.90 ± 0.42 vs. 0.35 ± 0.30 mmol/L; P = 0.001) and absolute synthesis rates (1.03 ± 0.55 vs. 0.50 ± 0.69 mmol/L/day; P = 0.01), but not fractional synthesis rates (114 ± 45 vs. 143 ± 82%/day; P = 0.07). The magnitudes of changes in patients with complications were greater for both GSH concentrations and absolute synthesis rates (P-values ≤ 0.01) compared to controls. There were no differences in GSH concentrations and synthesis rates between T2DM patients with and without complications (P-values > 0.1). Fasting glucose and HbA1c did not correlate with GSH concentration or synthesis rates (P-values > 0.17). CONCLUSIONS: Compared to non-diabetic controls, patients with T2DM have glutathione deficiency, especially if they have microvascular complications. This is probably due to reduced synthesis and increased irreversible utilization by non-glycemic mechanisms.

Isoprostanes, a marker of lipid peroxidation, may not be involved in the development of glucose intolerance.

We investigated whether isoprostanes, as a marker of lipid peroxidation, may be involved in the development of impaired glucose tolerance (IGT) or diabetes. Using a nested case-control study, we tracked the changes in isoprostane levels, insulin sensitivity (IS) and beta-cell function (BCF) in Afro-Jamaicans who progressed to IGT and diabetes over 3.9 years. Anthropometry, glucose tolerance, insulin levels, blood pressure and urinary isoprostane concentration were measured at baseline and follow-up. IS and BCF were estimated by the method of homeostasis assessment. Fifty-two individuals who progressed to IGT or diabetes and 44 age, sex and body mass index (BMI) matched controls were studied. Progression to glucose intolerance was significantly related with baseline BCF (p< or =0.01), but not isoprostane levels or IS. Glucose concentrations (fasting and 2 h) on follow-up were significantly correlated to baseline IS, baseline BCF, follow-up IS and follow-up BCF (p-values<0.05). In multiple regression analysis, only follow-up IS and BCF (p-values< or =0.001) independently predicted fasting glucose and 2h glucose levels at follow-up. Isoprostanes were not significantly associated with IS or BCF (p-values>0.1). We concluded that isoprostanes may not be causally involved in the development of glucose intolerance, insulin resistance or deteriorating BCF.

High prevalence of dyslipidemia among primary care patients with hypertension and diabetes in Jamaica.

INTRODUCTION: The aim of the study was to determine the prevalence of dyslipidemia among primary care patients with hypertension and diabetes in Jamaica and the proportion of patients who achieve recommended targets. MATERIAL AND METHODS: An audit of 500 dockets of adult patients with chronic disease attending public primary care clinics in Jamaica was conducted between October and December 2013. Data were collected on patient characteristics including medical history, medications, anthropometry, and lipid profiles (since January 1, 2011). Lipid targets were based on the Ministry of Health 2007 management guidelines. Stepwise multivariable logistic regression analysis was performed to determine the predictors of achieving lipid targets. RESULTS: Four hundred and thirty-seven patient records had a lipid profile done and 90% of these had at least one abnormal lipid value. 15.3% of the patients achieved the low density lipoprotein cholesterol (LDL-C) target, 63.2% high density lipoprotein cholesterol (HDL-C), 85.1% triglycerides and 57.4% the total cholesterol target. Statins were prescribed for 49% and these patients were less likely to achieve LDL-C (OR = 0.57; 95% CI: 0.33-0.97; p = 0.04) or total cholesterol (OR = 0.21; 95% CI: 0.13-0.33; p < 0.001) targets. Patients over 80 years were more likely to achieve the LDL-C target (OR = 3.21; 95% CI: 1.64-6.28; p = 0.002) than those less than 50 years old. More men than women achieved total cholesterol targets (OR = 2.2; 95% CI: 1.4-3.6; p = 0.001). CONCLUSIONS: Dyslipidemia is widespread among primary care patients with hypertension and diabetes. The proportion of patients who achieve the respective lipid targets must be documented and routinely monitored and appropriate medication and lifestyle changes implemented to improve this.

Socioeconomic factors associated with severe acute malnutrition in Jamaica.

OBJECTIVES: Severe acute malnutrition (SAM) is an important risk factor for illness and death globally, contributing to more than half of deaths in children worldwide. We hypothesized that SAM is positively correlated to poverty, low educational attainment, major crime and higher mean soil concentrations of lead, cadmium and arsenic. METHODS: We reviewed admission records of infants admitted with a diagnosis of SAM over 14 years (2000-2013) in Jamaica. Poverty index, educational attainment, major crime and environmental heavy metal exposure were represented in a Geographic Information System (GIS). Cases of SAM were grouped by community and the number of cases per community/year correlated to socioeconomic variables and geochemistry data for the relevant year. RESULTS: 375 cases of SAM were mapped across 204 urban and rural communities in Jamaica. The mean age at admission was 9 months (range 1-45 months) and 57% were male. SAM had a positive correlation with major crime (r = 0.53; P < 0.001), but not with educational attainment or the poverty index. For every one unit increase in the number of crimes reported, the rate of occurrence of SAM cases increased by 1.01% [Incidence rate ratio (IRR) = 1.01 (95% CI = 1.006-1.014); P P<0.001]. The geochemistry data yielded no correlation between levels of heavy metals and the prevalence of malnutrition. CONCLUSION: Major crime has an independent positive association with severe acute malnutrition in Jamaican infants. This could suggest that SAM and major crime might have similar sociological origins or that criminality at the community level may be indicative of reduced income opportunities with the attendant increase in poor nutrition in the home.

Predictors of hyperglycaemic crises and their associated mortality in Jamaica.

The objective of the study was to determine the clinical characteristics and mortality of patients with hyperglycaemic hyperosmolar syndrome (HHS) and diabetic ketoacidosis (DKA) at a Jamaican tertiary care hospital. In a retrospective study of 1560 admissions for diabetes during the period 1998-2002, 980 dockets were reviewed and 164 individuals met the ADA diagnostic criteria for DKA or HHS. Patients with HHS were older than DKA patients (64.5 years [95% CI: 60.7-68.4] versus 35.9 years [95% CI: 30.2-41.6]), but were not more likely to be non-compliant with medications, infected, or male. Overall, 24% had a mixed DKA/HHS syndrome. Most DKA patients had type 2 diabetes (62%). Only 2% of HHS and 6% of DKA/HHS patients had type 1 diabetes. Syndrome specific mortality was: DKA 6.7%, HHS 20.3%, and DKA/HHS 25% (p for trend=0.013). Mortality increased significantly with age, especially in patients > or =50 years. Significant univariate predictors of mortality were altered mental status on admission, co-existing medical disease, increasing age, older age at onset of diabetes, acute stressors, and DKA/HHS. In multivariate models, only altered mental status was significant (OR=3.59; 95% CI: 1.24-10.41). Hence, hyperglycaemic crises in a Jamaican tertiary care hospital are associated with significant mortality especially in patients who are older or with altered mental status.

Developmental contributions to macronutrient selection: a randomized controlled trial in adult survivors of malnutrition.

BACKGROUND AND OBJECTIVES: Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition. METHODOLOGY: Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%. RESULTS: Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP. CONCLUSIONS AND IMPLICATIONS: Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain.

Timing of changes in interstitial and venous blood glucose measured with a continuous subcutaneous glucose sensor.

The objective of this study was to use a subcutaneous continuous glucose sensor to determine time differences in the dynamics of blood glucose and interstitial glucose. A total of 14 patients with type 1 diabetes each had two sensors (Medtronic/MiniMed CGMS) placed subcutaneously in the abdomen, acquiring data every 5 min. Blood glucose was sampled every 5 min for 8 h, and two liquid meals were given. A smoothing algorithm was applied to the blood glucose and interstitial glucose curves. The first derivatives of the glucose traces defined and quantified the timing of rises, peaks, falls, and nadirs. Altogether, 24 datasets were used for the analysis of time differences between interstitial and blood glucose and between sensors in each patient. Time differences between blood and interstitial glucose ranged from 4 to 10 min, with the interstitial glucose lagging behind blood glucose in 81% of cases (95% CIs 72.5 and 89.5%). The mean (+/-SD) difference between the two sensors in each patient was 6.7 +/- 5.1 min, representing random variation in sensor response. In conclusion, there is a time lag of interstitial glucose behind blood glucose, regardless of whether glycemia is rising or falling, but intersensor variability is considerable in this sensor system. Comparisons of interstitial and blood glucose kinetics must take statistical account of variability between sensors.

The relationship among circulating insulin-like growth factor (IGF)-I, IGF-binding proteins-1 and -2, and birth anthropometry: a prospective study.

Fetal IGF-I is a determinant of birth weight, but whether maternal IGF-I plays a significant role is controversial. We sought to examine the relationships among maternal IGF-I, IGF-binding protein (IGFBP)-1, and IGFBP-2, with maternal and newborn anthropometry, in a cohort of 325 nondiabetic pregnant women of African origin. Blood was collected for IGF-I, IGFBP-1, and IGFBP-2 at 9, 25, and 35 wk gestation and in cord blood at delivery. In the second and third trimesters, maternal IGF-I was significantly correlated (P < 0.005) with maternal body mass index and triceps skinfold thickness. Maternal IGFBP-1 and -2 had an inverse correlation (P < 0.0001), with maternal anthropometry. Maternal IGF-I at 35 wk, and fetal IGF-I by cord blood were significantly correlated with birth weight (P = 0.001 and 0.048, respectively). IGFBP-1 in the third trimester and cord blood were negatively correlated with birth weight (P = 0.012 and 0.002). In multiple regression analyses, maternal IGF-I at 35 wk, fetal IGF-I, maternal weight at the first antenatal visit, gender, and gestational age were significant independent factors in the determination of birth weight. In conclusion, maternal IGF-I levels, especially during late pregnancy, positively influence birth weight.

The effect of earlier puberty on cardiometabolic risk factors in Afro-Caribbean children.

An earlier onset of puberty is associated with increased cardiometabolic risk. We investigated whether this relation was independent of faster childhood growth or current size in an Afro-Caribbean birth cohort (n=259). Anthropometry was measured at birth and then 6-monthly. Tanner staging started at age 8 years. Cardiometabolic risk factors were measured at mean age 11.5 years. In boys, pubarchal stage and testicular size were associated with lower high-density lipoprotein cholesterol, higher systolic blood pressure, and higher homeostasis model assessment of insulin resistance score, but not after adjusting for current body mass index (BMI) or rate of growth (up to age 8 years). In girls, earlier menarche and greater breast development were associated with higher fasting glucose even after adjusting for current BMI or prior growth. Pubarchal stage was associated with systolic blood pressure, even after adjusting for current BMI and prior growth. We concluded that earlier puberty is independently associated with cardiometabolic risk in girls but not in boys.

Limitations of fasting indices in the measurement of insulin sensitivity in Afro-Caribbean adults.

BACKGROUND: Insulin sensitivity can be estimated using glucose disposal rate (M) measured during a hyperinsulinemic euglycemic clamp (HEC) or insulin sensitivity index (SI) derived from a frequently sampled intravenous glucose tolerance test (FSIVGTT). The commonly used homeostatic model assessment of insulin resistance (HOMA-IR) which utilizes fasting glucose and insulin has been validated against M across several populations (r = 0.5-0.8). This study sought to validate HOMA-IR against SI and M in an Afro-Caribbean population. FINDINGS: Sixty participants completed a 180-minute FSIVGTT and another 50 completed a 150-minute hyperinsulinemic euglycemic clamp. In both groups, HOMA-IR was calculated and anthropometry and body composition using dual energy x-ray absorptiometry (DEXA) were measured.FSIVGTT: The participants were 55% male, age 23.1 ± 0.05 years, BMI 24.8 ± 6.3 kg/m2 and % body fat 25.0 ± 15.2 (mean ± SD). HEC: The participants were 44% male, age 27.3 ± 8.1 years, BMI 23.6 ± 5.0 kg/m2 and % body fat 24.7 ± 14.2 (mean ± SD). While HOMA-IR, SI and M correlated with waist, BMI and % body fat (P-values < 0.01) there were no significant correlations between HOMA-IR with either SI or M-value (P-values > 0.2). CONCLUSIONS: In young Afro-Caribbean adults, HOMA-IR compared poorly with other measures of insulin sensitivity. It remains important to determine whether similar findings occur in a more insulin resistant population. However, HOMA-IR correlated with clinical measures of insulin sensitivity (i.e. adiposity), so it may still be useful in epidemiological studies.

Glucose metabolism in adult survivors of severe acute malnutrition.

CONTEXT AND OBJECTIVES: The clinical syndromes of severe acute malnutrition may have early life origins because children with marasmus have lower birth weight than those with kwashiorkor. We hypothesized that resultant metabolic effects may persist into adulthood. We investigated whether marasmus survivors (MS) are more insulin resistant and glucose intolerant than kwashiorkor survivors (KS). RESEARCH DESIGN AND SETTING: This was a case-control study in Jamaican adults. SUBJECTS: We performed oral glucose tolerance tests on 191 adults (aged 17-50 y; 52% male; body mass index 24.2 ± 5.5 kg/m(2)). There were 43 MS; 38 KS; 70 age-, sex-, and body mass index-matched community controls; and 40 age- and birth weight-matched controls. MEASUREMENTS: We measured insulin sensitivity with the whole-body insulin sensitivity index, and ß-cell function with the insulinogenic index and the oral disposition index. RESULTS: Fasting glucose was comparable across groups, but glucose intolerance was significantly more common in MS (19%) than in KS (3%), community controls (11%), and birth weight-matched controls (10%). The whole-body insulin sensitivity index was lower in MS than KS (P = .06) but similar between MS and controls. The insulinogenic index and oral disposition index were lower in MS compared with all three groups (P < .01). CONCLUSIONS: Marasmus survivors tend to be less insulin sensitive, but have significantly lower insulin secretion and are more glucose intolerant compared with kwashiorkor survivors and controls. This suggests that poor nutrition in early life causes ß-cell dysfunction, which may predispose to the development of diabetes.