Determination of the differences in 2-h plasma glucose values after ingestion of carbohydrate foods and oral glucose in Caribbean non-diabetic subjects.

It has been reported that mixed meals are used in clinics in developing and developed countries in screening and diagnosis of diabetes. Thus, we aimed to determine the differences in 2-h plasma glucose values after non-diabetic subjects ingested 75 g pure glucose and its equivalent content in frequently consumed carbohydrate foods in Caribbean subjects. Twenty-seven apparently healthy non-diabetic subjects (nine males, 18 females) consumed 75 g pure glucose and its carbohydrate equivalent in three ethnic test foods (bread, rice and roti) at 7 days apart. Plasma glucose and insulin levels were determined in blood samples collected before and after 60, 90, 120 and 150 min of ingestion of these foods. In comparison with each of the test foods, the postprandial 1-h and 2-h plasma glucose values and the 60, 90, 120 and 150 min incremental glucose concentrations after oral glucose load were significantly higher than the corresponding values for each of the test foods (all P<0.01). In spite of these higher postprandial glucose concentrations, the postprandial insulin responses following the oral glucose load and the test foods did not significantly differ at any time point (all P>0.05). However, the test food, roti, tended to stimulate higher absolute and incremental insulin secretions than pure glucose or any other test food (all P>0.05). Generally, the correlation between 2-h plasma glucose value after the ingestion of the pure glucose and each of the test foods was significant (all correlation coefficients were greater than 0.70, P<0.01). In conclusion, different ethnic mixed meals could serve as an alternative to glucose in routine screening and diagnosis of diabetes if its available carbohydrate content is known and quantified.

The effects of chronic S-nitrosoglutathoine adminstration on glucose tolerance in dog animal model

The nitric oxide donor S-nitrosoglutathione (GSNO) has been used to prevent platelet activation in patients with severe pre-eclampsia. The study assesses the chronic administration of GSNO on glucose metabolism in the dog animal model. GSNO (10 mg/kg) was administered intravenously for 14 days and the blood glucose concentration was determined by the glucose oxidase method. Oral glucose tolerance tests revealed an impaired glucose tolerance in the GSNO-treated dogs as reflected by elevated postprandial blood glucose concentrations at the 1.0 hour to 2.5 hour time interval (p < 0.05). The elevated blood glucose concentration was associated with a statistically significant decrease in plasma insulin concentration. The plasma insulin concentration at 1.0 hour in captopril-treated controls was 41.00 uIU/ml compared with 27.33 uIU/ml in GSNO-treated dogs (p < 0.05). In contrast, the plasma glucagon concentration was enhanced by the chronic adminstration of GSNO, as confirmed by a concentration of 75.00 ñ 6.06 pg/ml in GSNO-treated dogs compared with 49.50 ñ 4.64 pg/ml in captopril-treated controls at the 1.0 hour time interval. Linear regression analysis of the data revealed a highly significant and positive correlation between the blood glucose concentration and the plasma glucagon concentration (r = 0.739, p < 0.01). Similarly, a positive correlation existed between the blood glucose concentration and the plasma insulin concentration (r = 0.513, p = 0.307). We conclude that chronic in vivo adminstration of GSNO impairs the parameters of carbohydrate metabolism. Patients who are on protracted treatment with GSNO could be risk for the development of diabetes mellitus.(Au)

Defining diabetes mellitus - is the matter resolved?

OBJECTIVE: To investigate the theoretical distribution of incident cardiovascular events and retinopathy with respect to 2-hour glucose concentration in a population-based study of Jamaican adults and the implications of these distributions for the diagnosis of diabetes mellitus. METHODS: The American Diabetes Association and WHO diagnostic criteria for diabetes are based on the risk of microvascular complications of diabetes mellitus. There appears to be a threshold glucose concentration for incidence of retinopathy and nephropathy. However, no such threshold is apparent for macrovascular complications of diabetes mellitus. We applied risk estimates of incident cardiovascular disease associated with increasing 2-hour glucose concentration derived from a metaregression analysis of 20 studies to the distribution of 2-hour glucose concentration in the Spanish Town Survey. A sample of 1907 adults aged 25-74 years was recruited by door-to-door canvassing. Oral glucose tolerance testing was conducted after an overnight fast. The theoretical distribution of cardiovascular disease in the Spanish Town Survey was derived and compared with the theoretical distribution of retinopathy based on risk estimates from studies of Pima Indians. RESULTS: The prevalence of diabetes mellitus (2-hour glucose = 11.1 mmol/l) was 13.2 percent and 12.5 percent in subjects who had glucose concentrations between 8 and 11 mmol/l [approximately equivalent to range for impaired glucose tolerance (IGT)]. All cases of incident retinopathy would occur above 2-hour glucose concentration of 11.1 mmol/l. Only 38.5 percent of incident cases of cardiovascular disease would occur in this range while a further 13 percent would occur in the IGT range. Half of the cases would therefore occur in individuals considered to be normoglycaemic. CONCLUSION: The current WHO diagnostic criteria for diabetes mellitus identify all subjects at risk for microvascular complications of diabetes. However, they may miss as many as half of those at risk for cardiovascular disease, the leading cause of morbidity and mortality in diabetes mellitus.(Au)

Fat distribution and glucose metabolism in pregnancy: an anthropometric study of Barbadian women

Two hundred and fifty women were studied to evaluate the effects of maternal growth on glucose and insulin metabolism during the pregnancy. Participants were recruited from the antenatal clinic at the Queen Elizabeth Hospital, Barbados, if they booked by 16 weeks' gestation. Anthropometric indices, including skinfold thickness, weight, height and hip circumference, were measured at recruitment, and participants subjected to a 75-gm oral glucose tolerance test (WHO criteria) at 18 weeks' gestation. Fasting blood samples were collected for plasma lipids, venous plasma glucose (VPG), serum insulin, c-peptide and glycosylated haemoglobin. Samples were taken at 1 and 2 hours post glucose load for VGP (fasting: p=0.003; 1 hour: p=0.008; 2 hour: p=0.026) and fasting insulin levels (p=0.02). High mean hip circumference at booking was associated with raised VPG (fasting:p=0.07; 1 hour: p=0.04; 2hour: p=0.16) and fasting serum insulin (p<0.001). Fat distribution, rather than global obesity per se, may be an important factor influencing glucose and insulin metabolism during pregnancy (AU)

Insulin therapy and nephropathy - abstract

There is a four-fold increase in the risk of diabetic nephropathy in patients with poor glycaemic control. Glycaemic control, soon after the diagnosis of diabetes mellitus (Type-1, IDDM), may reduce the elevated glomerular filtration rate (GFR). Recently, it has been shown that the introduction of insulin may reduce the exaggerated GFR response of newly diagnosed IDDM to infusion of amino acids to normal, and at the same time cause reversal of renal hypertrophy. Long-term studies suggest that reduction in microalbuminuria and progression to clinical nephropathy can be prevented with tight glucose control, compared to patients with lesser glucose control. In well-established nephropathy, however, there is little evidence that glycaemic control has any impact on progression to renal failure (AU)

Hypoglycaemia in chronic renal failure

Persistant symptomatic hypoglycaemia developed in a 26-year-old woman with chronic renal failure. Several factors, including the use of sulfametethroxaole, recent peritoneal dialysis, and poor nutrition may have combined with defective glycogenosis and gluconeogenesis present in chronic renal failure to play a role in its aetiology. Increased awareness of this condition is necessary because chronic renal failure is common in the Caribbean. (AU)

Intrapartum infusion of oxytocin and glucose water and neonatal jaundice

Two hundred and seventy-eight deliveries were studied prospectively to determine the association between the use of oxytocin during labour and the incidence of neonatal jaundice. Jaundice was seen significantly more often in neonates following maternal infusion of oxytocin in dextrose water (OT) or dextrose water alone (DW) as compared to those whose mothers did not receive either. No significant difference was seen in the incidence of jaundice between OT or DW groups. Mean umbilical cord serum sodium levels were significantly lower in the OT and DW group neonates who became jaundiced, as compared to the rest of the neonates in the same group and the control group. Sixty per cent of the jaundiced neonates in the OT as well as the DW group had frank hyponatremia as compared to only 8 percent in the control group. These findings support a probable causative association between hyponatremia at birth and neonatal jaundice in the deliveries following dextrose water and/or oxytocin infusion (AU)

Reduction by morphine of human prosprandial insulin release is secondary to inhibition of gastrointestinal motility

The effect of morphine (0.1 mg/kg) on insulin secretion stimulated by oral, intraduodenal, or intravenous administration of glucose was studied in seven healthy volunteers. When glucose was given intravenously, morphine had no effect on plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), or pancreatic glucagon. Following oral glucose, morphine slowed gastric emptying and reduced plasma concentrations of glucose, insulin, and GIP. During intraduodenal infusion of glucose, insulin concentrations of plasma were also decreased by morphine, an effect best explained by decreased small intestinal transit with delayed absorption of glucose and delayed release of GIP. We conclude that clinically relevant doses of morphine have no direct effect on insulin secretion and that the changes observed were secondary to slowed gastric emptying and small intestinal transit (AU)

Intrapartum infusion of aquenous glucose solution, transplacental hyponatraemia and risk of neonatal jaundice

Cord serum sodium levels in three groups of 278 singleton infants, born vaginally at term, were correlated with the incidence of jaundice (serum bilirubin o85æmol/1) in the first 3 days of life. Of the 278 infants, 87 were born to mothers who were given infusions of 5 percent or 10 percent glucose in water during labour (group I), 90 were born to mothers who received glucose solution as a vehicle for oxytocin (group II), and 101 to mothers who did not receive any intravenous fluid therapy (control group). Jaundice was seen significantly more frequently in groups I (28/87, 32 percent) and II infants (30/90, 33 percent) than in the control group (12/101, 12 percent) (P<0.01), but when analysed in relation to cord serum sodium levels, the prevalence of jaundice in the normonatraemic infants (serum sodium o131 mmol/1) was similar in the three groups. On the other hand, in groups I and II jaundice occurred about 3.5 times more frequently in the hyponatraemic infants (group I (17/32, 53 percent) and II (20/39, 51 percent) than in the normonatraemic infants (P<0.01). The difference was not associated with any other perinatal or neonatal characteristic.(AU)

The influence of the sympathoadrenal system on insulin release in protein-energy malnutrition (PEM)

Low insulin release has been observed in PEM; however, structural damage of the endocrine pancreas is not considered a major causative factor. Although PEM can be considered a stress situation, and catecholamines are known to be inhibitors of insulin release, little work has been done on the role of the sympathoadrenal system on insulin release in PEM. Control rats (132ñ2.6 g) and malnourished rats (53ñ0.55 g) fed on lab chow for 21-28 days after weaning were anaesthethized with 50 mg/kg body weight sodium-pentobarbital intraperitoneally, and blood for insulin radioimmunoassay sampled from the portal vein. Fasting insulin levels in 30 malnourished and 30 control rats were 1.6ñ0.4 uU.ml and 3.93ñ0.26 uU/ml respectively (p<0.001). The two groups of animals showed a significant difference in insulin output in response to glucose load. After collecting fasting blood in malnourished and control rats, an alpha-receptor blocker, phentolamine (0.25 mg/kg body weight), was administered through the inferior vena cava and blood sampled over a period of 2, 5, 10, 20, 30, 45 and 60 minutes. The area under the curves showed no difference in magnitude of insulin release in the two groups. Administering O-methyltyrosine (80 mg/kg body weight) for four days before sacrifice, catecholamine synthesis was blocked in 30 control and 30 malnourished rats. The fasting insulin levels in control and malnourished rats were 9.83ñ0.86 uU/ml and 9.63ñ0.6 uU/ml respectively. The insulin response to intravenous glucose challenge in the control and malnourished rats treated with O-methyl tyrosine for four days before sacrifice was exaggerated during the first phase of release and was of the same magnitude in both groups as compared with rats without drug treatment. Fifteen control and 15 malnourished rats were treated with tranquilizer, diazepam (0.15 mg/kg body weight), over a period of 10-14 days. Fasting insulin levels in the malnourished and control rats were 3.17ñ0.16 uU/ml and 4.61ñ0.11 uU/ml respectively, a significant increase (p<0.001) in the malnourished animals compared with rats without drug treatment. The plasma calcium and potassium levels, which are known to influence insulin release, showed no significant difference between control and malnourished groups. Finally, the histological examination of the islets by light microscopy showed the presence of "normal" B cells in both the malnourished and control rats. These results show that the sympathoadrenal system is one of the factors causing low insulin release in PEM. Although in PEM low insulin output is a form of adaptation to life, high insulin levels are required during treatment. The anabolic effect of insulin might, therefore, be enhanced if PEM patients were subjected to less stress during the period of treatment (AU)

Composition of oral solutions prepared by Jamaican mothers for treatment of diarrhoea

Oral rehydration with sucrose-electrolyte solutions is now established as a safe and effective way to treat dehydrated children in hospital. In Jamaica, oral rehydration with World Health Organization approved packets of glucose-electrolyte salts supplied by the United Nations International Children's Emergency Fund has been successfully introduced in the main children's hospitals in Kingston. However, because of the difficulty of supplying packets to scattered urban and rural community clinics, mothers are advised by health personnel as well as on radio and television programmes to prepare various homemade sugar-salt solutions to treat children with diarrhoea at home. The composition of solutions prepared by mothers varies dangerously. To reduce errors, a double ended spoon has been designed to help mothers to make up solutions more accurately. The value of the spoon has been established under the most favourable conditions. To obtain the maximum rate of absorption of water and electrolytes in dehydrated children, the oral solution should approximate closely to the WHO recommended solution which contains glucose 110 mmol/l (sucrose 210 mmol/l), sodium 90mmol/l, potassium 20 mmol/l, chloride ions 80 mmol/l, and bicarbonate 30 mmol/l. We compared the composition of salt-sugar solutions prepared by Jamaican mothers according to current health education and those prepared by means of the double-ended spoon. (AU)

Physiological mechanism and pathogenesis of weanling diarrhea

Quantitative aerobic and anaerobic bacteriological studies of the upper and lower jejunum were performed in six malnourished children without diarrhea and in a group of five malnourished children with weanling diarrhea. A third group of children was tested after prolonged treatment in the hospital. All three groups of children had small numbers of mixed aerobic and anaerobic bacteria in the upper and lower intestine; only four children had a total bacterial count above 10[4]/g, and there was no correlation between the numbers or type of organinsms and the nutritional state of the child. Jejunal perfusion studies showed that the children with weanling diarrhea had a marked jejunal accumulation of fluid, i.e., net secretion, similar to that seen in cholera. Malnourished or treated children without diarrhea did not show this abnormality. Glucose promoted water absorption even in children with gastroenteritis who had reduced glucose absorption rates. No enterotoxin-producing organisms were isolated to account for these functional changes. Treating cases of weanling diarrhea with low concentrations of oral glucose should promote positive water and electrolyte balance, but this effect will be limited by the degree of glucose malabsorption in the individual child. (Summary)

Glucose tolerance and insulin sensitivity in malnourished children

In malnourished, compared with recovered children, fasting blood glucose concentrations were low and there was impared peripheral glycolysis as shown by a failure of blood lactate to raise after glucose was injected intravenously. Homogenates of muscle biopsies from malnourished and recovered children produced equal amounts of lactate when incubated anaerobically with various substrates, but when compared with homogenates of biopsies from normal children the pattern suggested an impairment of glycolysis. The rate of glucose disappearance after intravenous glucose was slow in the malnourished child and there was possibly diminished sensitivity to exogenous insulin. Isocaloric diets relatively high or low in fat were fed to children who had recovered from malnutrition. Glucose tolerance, insulin sensitivity, fasting plasma insulin and insulin response to intravenous glucose were all the same in children on either diet. (AU)

The effect of phenyl ethyl biguanide in vivo and in vitro on gluconeogenesis and ammonia production in rats

The drug phenyl ethyl biguanide (PEBG) was used in vivo and in vitro to study further the relationship between renal gluconeogenesis and ammonia production in the rat. When PEBG was injected intraperitoneally into the rats, it caused a decrease in urinary ammonia in spite of a greater degree of systemic acidosis. PEBG injections also blocked the increase in glucose and ammonia production by renal cortical slices from rats which had been made acidotic by oral administration of ammonium chloride 2h previously. With increasing concentrations of PEBG in vitro, there was inhibition of gluconeogenesis and ammonia production from glutamine and glutamate as substrates. The two processes were equally inhibited when glutamate was used as substrate but with glutamine, gluconeogenesis was more inhiblted than ammonia production. The inhibition of renal gluconeogenesis by PEBG in vitro was similar when succinate, oxaloacetate, fructose, glutamine and glutamate were used as substrates. The results show that PEBG does not inhibit gluconeogenesis by blocking a specific site in the gluconeogenic pathway. In addition, further proof is provided of the physiological interrelationship of renal ammonia production and gluconeogenesis (Summary)