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There is limited information as to whether people who experience severe acute malnutrition (SAM) as young children are at increased risk of overweight, high body fat and associated chronic diseases in later life. We followed up, when aged 7-12 years, 100 Zambian children who were hospitalised for SAM before age 2 years and eighty-five neighbourhood controls who had never experienced SAM. We conducted detailed anthropometry, body composition assessment by bioelectrical impedance and deuterium dilution (D2O) and measured blood lipids, Hb and HbA1c. Groups were compared by linear regression following multiple imputation for missing variables. Children with prior SAM were slightly smaller than controls, but differences, controlling for age, sex, socio-economic status and HIV exposure or infection, were significant only for hip circumference, suprailiac skinfold and fat-free mass index by D2O. Blood lipids and HbA1c did not differ between groups, but Hb was lower by 7·8 (95 % CI 0·8, 14·7) g/l and systolic blood pressure was 3·4 (95 % CI 0·4, 6·4) mmHg higher among the prior SAM group. Both anaemia and high HbA1c were common among both groups, indicating a population at risk for the double burden of over- and undernutrition and associated infectious and chronic diseases. The prior SAM children may have been at slightly greater risk than the controls; this was of little clinical significance at this young age, but the children should be followed when older and chronic diseases manifest.

Background: The prevalence, pathology, and existence of malnutrition-associated diabetes remain uncertain, especially with respect to adult-acquired undernutrition., Objective: The aim was to investigate the association of prior undernutrition (low BMI, in kg/m2), acquired in adulthood and insulin during an oral glucose tolerance test (OGTT)., Methods: We followed up 630 adults recruited 7-14 y previously for other studies. Plasma insulin was measured fasting and at 30 and 120 min during an OGTT. The main exposure was BMI measured 7-14 y prior. The main outcome of interest was plasma insulin, controlling for time during the OGTT using generalized estimating equations, and exploratory outcomes were early insulin response (relative change in insulin and glucose from 0-30 min) and relative insulin and glucose AUCs from 0 to 120 min. Current confounding factors were age, sex, BMI, HIV, socioeconomic status, and physical activity., Results: In unadjusted analyses, increasing severity of prior malnutrition was associated with lower insulin concentration. In multivariate adjusted analyses, only current BMI was a strong predictor of overall insulin concentration. Associations with prior BMI of insulin responses accounting for glucose were also seen in unadjusted but not adjusted analyses. For insulin concentration but not the outcomes accounting for glucose, there was a sex interaction with prior BMI such that only men had lower insulin if previously malnourished: insulin (pmol/L) at 120 min was 311 (95% CI: 272, 351) for prior BMI ≥18.5, 271 (95% CI: 221, 321) for prior BMI 17.0-18.5, and 237 (95% CI: 194, 297) for prior BMI <17.0; P = 0.03. HIV status showed limited and variable associations with insulin., Conclusions: Insulin concentration, fasting and during an OGTT, was normalized in women more than in men several years after adult malnutrition. Chronic malnutrition, as indicated by low prior and current BMI, may contribute to diabetes through low insulin secretion., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Malnourished HIV-infected patients starting antiretroviral therapy (ART) are at high risk of early mortality, some of which may be attributed to altered electrolyte metabolism. We used data from a randomised controlled trial of electrolyte-enriched lipid-based nutritional supplements to assess the association of baseline and time-varying serum phosphate and K concentrations with mortality within the first 12 weeks after starting ART. Baseline phosphate results were available from 1764 patients and there were 9096 subsequent serum phosphate measurements, a median of 6 per patient. For serum K there were 1701 baseline and 8773 subsequent measures, a median of 6 per patient. Abnormally high or low serum phosphate was more common than high or low serum K. Controlling for other factors found to affect mortality in this cohort, low phosphate which had not changed from the previous time interval was associated with increased mortality; the same was not true for high phosphate or for high or low K. Both increases and decreases in serum electrolytes from the previous time interval were generally associated with increased mortality, particularly in the electrolyte-supplemented group. The results suggest that changes in serum electrolytes, largely irrespective of the starting point and the direction of change, were more strongly associated with mortality than were absolute electrolyte levels. Although K and phosphate are required for tissue deposition during recovery from malnutrition, further studies are needed to determine whether specific supplements exacerbate physiologically adverse shifts in electrolyte levels during nutritional rehabilitation of ill malnourished HIV patients.

Background: A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation., Methods: We analysed potential risk factors for mortality of Zambian and Tanzanian participants enrolled in the NUSTART clinical trial. Malnourished adults (n = 1815; body mass index [BMI] <18.5 kg/m 2 ) were recruited at referral to ART and randomised to receive different nutritional supplements. Demographics, measures of body composition, blood electrolytes and clinical conditions were investigated as potential risk factors using Poisson regression models., Results: The mortality rate was higher in the period from referral to starting ART (121 deaths/100 person-years; 95 % CI 103, 142) than during the first 12 weeks of ART (66; 95 % CI 57, 76) and was not affected by trial study arm. In adjusted analyses, lower CD4 count, BMI and mid-arm circumference and raised C-reactive protein were associated with an increased risk of mortality throughout the study. Male sex and lower hand-grip strength carried an increased risk in the pre-ART period. Participants on tuberculosis treatment at referral had a lower mortality rate (adjusted Rate Ratio 0.44; 95 % CI 0.31, 0.63)., Conclusion: Among malnourished ART-eligible adults, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests undiagnosed tuberculosis is a contributor to mortality in this population., Trial Registration: Pan African Clinical Trials Registry, PACTR201106000300631 ; registered on 1st June 2011.

Background/objectives: The effects of inflammation on nutritional rehabilitation after starting antiretroviral therapy (ART) are not well understood. We assessed the relationship between inflammation and body composition among patients enrolled in the Nutritional Support for African Adults Starting Antiretroviral therapy (NUSTART) trial in Tanzania and Zambia from 2011 to 2013., Subjects/methods: HIV-infected, ART-eligible adults with body mass index (BMI) of <18.5 kg/m(2) enrolled in the NUSTART trial were eligible for this study. Anthropometric and body composition data were collected at recruitment and 6 and 12 weeks post ART and C-reactive protein (CRP) was measured at recruitment and 6 weeks. The relationships between CRP and body composition were assessed using multiple regression., Results: Of the 1815 trial participants, 838 (46%) had baseline and 6-week CRP measurements. Median age was 36 years, 55% were females and median CD4 count was 135 cells/μl. A one-log reduction in CRP at 6 weeks was associated with increased mid-upper arm circumference (0.45 cm; 95% CI: 0.30, 0.61), calf circumference (0.38 cm; 0.23, 0.54), waist circumference (0.98 cm; 0.59, 1.37), BMI (0.37 kg/m(2); 0.24, 0.50) and fat-free mass (0.58 kg; 0.26, 0.91), but not with fat mass (0.09 kg; -0.17, 0.34). Fat-free mass gains persisted at 12 weeks and were more closely associated with 6-week CRP values than with baseline values., Conclusions: Reduction in CRP shortly after ART initiation was associated with higher fat-free mass gains. Further studies are warranted to determine whether interventions to reduce systemic inflammation will enhance gains in fat-free mass.

Background: Low intakes of good-quality complementary foods (CFs) contribute to undernutrition and consequently negatively affect health, growth, and development. Lipid-based nutrient supplements (LNSs) are designed to ensure dietary adequacy in micronutrients and essential fatty acids and to provide some energy and high-quality protein. In populations in which acute energy deficiency is rare, the dose-dependent effect of LNSs on CF intakes is unknown., Objective: The objective of this study was to evaluate the difference in energy and macronutrient intakes from CF between a control (no supplement) group and 3 groups that received 10, 20, or 40 g LNS/d., Methods: We collected repeated interactive 24-h dietary recalls from caregivers of rural Malawian 9- to 10-mo-old infants (n = 748) to estimate dietary intakes (LNS and all non-breast-milk foods) of energy and macronutrients and their dietary patterns. All infants were participating in a 12-mo randomized controlled trial to investigate the efficacy of various doses of LNS for preventing undernutrition., Results: Dietary energy intakes were significantly higher among infants in the LNS intervention groups than in the control group (396, 406, and 388 kcal/d in the 10-, 20-, and 40-g LNS/d groups, respectively, compared with 345 kcal/d; each pairwise P < 0.05), but no significant differences were found in energy intakes between groups who were administered the different LNS doses (10 g LNS/d compared with 20 g LNS/d: P = 0.72; 10 g LNS/d compared with 40 g LNS/d: P ≥ 0.67; 20 g LNS/d compared with 40 g LNS/d: P = 0.94). Intakes of protein and fat were significantly higher in the LNS intervention groups than in the control group. No significant intergroup differences were found in median intakes of energy from non-LNS CFs (357, 347, and 296 kcal/d in the 10-, 20-, and 40-g LNS/d groups, respectively, compared with 345 kcal/d in the control group; P = 0.11)., Conclusion: LNSs in doses of 10-40 g/d increase intakes of energy and macronutrients among 9- to 10-mo-old Malawian infants, without displacing locally available CFs. This trial was registered at clinicaltrials.gov as NCT00945698., (© 2016 American Society for Nutrition.)

Background: The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive., Objective: We hypothesized that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnourished patients starting ART and that vitamin and mineral supplementation would improve appetite and permit nutritional recovery., Design: The randomized controlled Nutritional Support for Africans Starting Antiretroviral Therapy trial was conducted in Mwanza, Tanzania, and Lusaka, Zambia. ART-naive adults referred for ART and with body mass index <18.5 kg/m received lipid-based nutritional supplements either without (LNS) or with added vitamins and minerals (LNS-VM), beginning before ART initiation. Participants were given 30 g/d LNS from recruitment until 2 weeks after starting ART and 250 g/d from weeks 2 to 6 of ART., Results: Of 1815 patients recruited, 365 (20%) died during the study and 813 (45%) provided data at 12 weeks. Controlling for baseline values, anthropometric measures were consistently higher at 12-week ART in the LNS-VM than in the LNS group but statistically significant only for calf and mid-upper arm circumferences and triceps skinfold. Appetite did not differ between groups. Using piecewise mixed-effects quadratic models including all patients and time points, the main effects of LNS-VM were seen after starting ART and were significant for weight, body mass index, and mid-upper arm circumference., Conclusions: Provision of high levels of vitamins and minerals to patients referred for ART, delivered with substantial macronutrients, increased nutritional recovery but did not seem to act through treatment group differences in appetite.

Objective: The Nutritional Support for Africans Starting Antiretroviral Therapy (NUSTART) trial was designed to determine whether nutritional support for malnourished HIV-infected adults starting antiretroviral therapy (ART) can improve early survival. Appetite is related to health outcomes in this population, but the optimal appetite metric for field use is uncertain. We evaluated two measures of appetite with the goal of improving understanding and treatment of malnutrition in HIV-infected adults., Design: Longitudinal cohort study embedded in a clinical trial of vitamin and mineral-fortified, v. unfortified, lipid-based nutritional supplements., Setting: HIV clinics in Mwanza, Tanzania and Lusaka, Zambia., Subjects: Malnourished (BMI<18.5 kg/m2) HIV-infected adults starting ART., Results: Appetite measurements, by short questionnaire and by weight of maize porridge consumed in a standardized test, were compared across time and correlated with changes in weight. Appetite questionnaire scores, from polychoric correlation, and porridge test results were normally distributed for Tanzanians (n 187) but clustered and unreliable for Zambians (n 297). Among Tanzanian patients, the appetite score increased rapidly from referral for ART, plateaued at the start of ART and then increased slowly during the 12-week follow-up. Change in appetite questionnaire score, but not porridge test, correlated with weight change in the corresponding two-week intervals (P=0.002) or over the whole study (P=0.05) but a point estimate of hunger did not predict weight change (P=0.4)., Conclusions: In Tanzania change in appetite score correlated with weight change, but single point measurements did not. Appetite increases several weeks after the start of ART, which may be an appropriate time for nutritional interventions for malnourished HIV-infected adults.

Background: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality., Methods: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m² who were referred for ART based on CD4 count <350 cells/μL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART., Results: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/μL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02)., Conclusions: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients., Trial Registration: PACTR201106000300631, registered on 1st June 2011.