c-peptide and Malnutrition

Twelve years following gastric bypass surgery, a cachectic 69-year-old woman presented with both fasting and postprandial hypoglycaemia. Postprandial symptoms were relieved by dietary modification and acarbose, as is common in such cases. During a supervised fast, symptomatic hypoglycaemia occurred. Concurrent laboratory testing showed suppression of plasma insulin, c-peptide, proinsulin and insulin-like growth factor II. However, beta-hydroxybutyrate was also low, surprising given insulin deficiency. Elevated plasma free fatty acid (FFA) concentrations suggested that lipolysis was not impaired, making cachexia/malnutrition a less likely cause of hypoglycaemia. The apparent diagnosis was failure to counter-regulate-subsequent plasma carnitine measurements showed carnitine deficiency which presumably prevented FFA transport across mitochondrial membranes for ketogenesis. Repletion with high-dose oral carnitine supplements effected resolution of fasting hypoglycaemia.

Topics: Aged; C-Peptide; Carnitine; Fasting; Female; Gastric Bypass; Humans; Hypoglycemia; Insulin; Malnutrition

Poor fetal growth, also known as intrauterine growth restriction (IUGR), is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX) or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN). Physiological (glucose and insulin tolerance), morphometric (automated tissue image analysis) and transcriptomic (quantitative PCR) approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

Topics: Adipose Tissue; Analysis of Variance; Animals; Blood Glucose; Blotting, Western; Body Weights and Measures; C-Peptide; Corticosterone; Dexamethasone; DNA Primers; Female; Fetal Growth Retardation; Gene Expression Profiling; Insulin; Insulin Resistance; Islets of Langerhans; Leptin; Malnutrition; Pregnancy; Prenatal Exposure Delayed Effects; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

Surveys in northern Ethiopia have demonstrated that apparent type 1 diabetes occurs more frequently than elsewhere in Africa and, indeed, in other parts of the world. We therefore investigated in detail a cohort of diabetic patients from this region to clarify the nature of this type of diabetes.. All patients attending the diabetic clinic at Mekelle Hospital in the Tigray region of northern Ethiopia were investigated over a 6 week period. Clinical, demographic and anthropometric data were collected, as well as measurements of HbA(1c), fasting lipid profile, fasting serum C-peptide and serum markers of beta cell autoimmunity, i.e. islet antigen-2 and GAD antibodies (GADA).. Of 105 patients seen, 69 (66%) were on insulin treatment and had been from or close to diagnosis. Their median age and diabetes duration were 30 and 5 years, respectively, with a male excess of 2:1. Median BMI was 20.6 kg/m². Despite these clinical characteristics suggestive of type 1 diabetes, only 42 of 69 (61%) patients were C-peptide-negative and 35% GADA-positive. Overall, 38 (36%) of the total group (n = 105) had immunological or C-peptide characteristics inconsistent with typical type 1 or type 2 diabetes. The clinical characteristics, local prevalence of undernutrition, and GADA and C-peptide heterogeneity suggest a malnutrition-related form of diabetes.. Not all patients in northern Ethiopia with apparent type 1 diabetes appear to have the form of disease seen in Europids; their disease may, in fact, be related to malnutrition.

Topics: Adult; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Ethiopia; Female; Glutamate Decarboxylase; Humans; Insulin; Male; Malnutrition; Middle Aged

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity, hyperleptinemia, insulin resistance, and type 2 diabetes. Although the mechanisms are unclear, this "programming" has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition (UN) during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Using this model of maternal UN, we have recently shown that neonatal leptin treatment in females reverses the postnatal sequelae induced by developmental programming. To examine possible gender-related effects of neonatal leptin treatment, the present study investigated the effect of neonatal leptin treatment on the metabolic phenotype of adult male offspring. Leptin treatment (recombinant rat leptin, 2.5 microg/g.d, sc) from postnatal d 3-13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring. Neonatal leptin treatment of male offspring from normally nourished mothers caused an increase in diet-induced weight gain and related metabolic sequelae, including hyperinsulinemia and increased total body adiposity compared with saline-treated controls. This occurred without an increase in caloric intake. These effects were specific to offspring of normal pregnancies and were not observed in offspring of mothers after UN during pregnancy. In the latter, neonatal leptin treatment conferred protection against the development of the programmed phenotype, particularly in those fed the chow diet postnatally. These data further reinforce the importance of leptin in determining long-term energy homeostasis, and suggest that leptin's effects are modulated by gender and both prenatal and postnatal nutritional status.

Topics: Adipose Tissue; Animals; Animals, Newborn; Blood Glucose; Bone Density; C-Peptide; Eating; Female; Insulin; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Pregnancy; Rats; Rats, Wistar; Weight Gain