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.

Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities.

The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.

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.