Insulin storage in hot climates without refrigeration: temperature reduction efficacy of clay pots and other techniques.

AIM: Insulin loses potency when stored at high temperatures. Various clay pots part-filled with water, and other evaporative cooling devices, are used in less-resourced countries when home refrigeration is unavailable. This study examined the cooling efficacy of such devices. METHODS: Thirteen devices used in Sudan, Ethiopia, Tanzania, Mali, India, Pakistan and Haiti (10 clay pots, a goat skin, a vegetable gourd and a bucket filled with wet sand), and two identical commercially manufactured cooling wallets were compared. Devices were maintained according to local instructions. Internal and ambient temperature and ambient humidity were measured by electronic loggers every 5 min in Khartoum (88 h), and, for the two Malian pots, in Bamako (84 h). Cooling efficacy was assessed by average absolute temperature difference (internal vs. ambient), and % maximal possible evaporative cooling (allowing for humidity). RESULTS: During the study period, mean ambient temperature and humidity were 31.0°C and 32.0% in Khartoum and 32.9°C and 39.8% in Bamako. All devices reduced the temperature (P < 0.001) with a mean (sd) reduction from 2.7 ± 0.5°C to 8.3 ± 1.0°C, depending on the device. When expressed as % maximal cooling, device efficacy ranged from 20.5% to 71.3%. On cluster analysis, the most efficacious devices were the goat skin, two clay pots (from Ethiopia and Sudan) and the suspended cooling wallet. CONCLUSIONS: Low-cost devices used in less-resourced countries reduce storage temperatures. With more efficacious devices, average temperatures at or close to standard room temperature (20-25°C) can be achieved, even in hot climates. All devices are more efficacious at lower humidity. Further studies are needed on insulin stability to determine when these devices are necessary.

Financial costs for families of children with Type 1 diabetes in lower-income countries.

AIMS: To assess the direct costs of necessary consumables for minimal care of a child with Type 1 diabetes in countries where the public health system does not regularly provide such care. METHODS: Supply costs were collected between January 2013 and February 2015 from questionnaires submitted by centres requesting International Diabetes Federation Life for a Child Program support. All 20 centres in 15 countries agreed to the use of their responses. Annual costs for minimal care were estimated for: 18 × 10 ml 100 IU/ml insulin, 1/3 cost of a blood glucose meter, two blood glucose test strips/day, two syringes/week, and four HbA1c tests/year. Costs were expressed in US dollars, and as % of gross national income (purchasing power parity) per capita. RESULTS: The ranges (median) for the minimum supply costs through the private system were: insulin 10 ml 100 IU/ml equivalent vial: $5.10-$25 ($8.00); blood glucose meter: $15-$121 ($33.33); test strip: $0.15-$1.20 ($0.50); syringe: $0.10-$0.56 ($0.20); and HbA1c : $4.90-$20 ($9.75). Annual costs ranged from $255 (Pakistan) to $1,185 (Burkina Faso), with a median of $553. Annual % gross national income costs were 12-370% (median 56%). For the lowest 20% income earners the annual cost ranged 20-1535% (median 153%). St Lucia and Mongolia were the only countries whose governments consistently provided insulin. No government provided meters and strips, which were the most expensive supplies (62% of total cost). CONCLUSIONS: In less-resourced countries, even minimal care is beyond many families' means. In addition, families face additional costs such as consultations, travel and indirect costs. Action to prevent diabetes-related death and morbidity is needed.

Prevalence and incidence of clinically recognized cases of Type 1 diabetes in children and adolescents in Rwanda, Africa.

AIMS: To determine prevalence and incidence estimates for clinically recognized cases of Type 1 diabetes from the Life For a Child Program (LFAC) with onset < 26 years in six representative districts, and the capital, of Rwanda. METHODS: Cases were identified from the LFAC registry and visits to district hospitals. Denominators were calculated from district-level population surveys. Period prevalence data were collected from 1 August 2011 to 31 July 2012 and annual incidence rates were calculated, retrospectively, for 2004-2011. Ninety-five per cent confidence intervals (95% CI) were calculated using a Poisson distribution. RESULTS: The prevalence of known Type 1 diabetes in seven districts in Rwanda for ages < 26 years was 16.4 [95% CI 14.6-18.4]/100 000 and for < 15 years was 4.8 [3.5-6.4]/100 000. Prevalence was higher in females (18.5 [15.8-21.4]/100 000) than males (14.1 [11.8-16.7]/100 000; P = 0.01) and rates increased with age. The annual incidence rate for those < 26 years was stable between 2007 and 2011 with a mean incidence over that time of 2.7 [2.0-3.7]/100 000 ( < 15 years = 1.2 [0.5-2.0]/100 000). Incidence rates were higher in females than males and peaked in males at ages 17 and 22 years and in females at age 18 years. CONCLUSIONS: Our report of known Type 1 diabetes cases shows lower incidence and prevalence rates in Rwanda than previously reported in the USA and most African countries. Incidence of recognized cases has increased over time, but has recently stabilized. However, the likelihood of missed cases due to death before diagnosis and misdiagnosis is high and therefore more definitive studies are needed.

Tropical distal renal tubular acidosis: clinical and epidemiological studies in 78 patients.

BACKGROUND: Distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene encoding the erythroid and kidney isoforms of anion exchanger 1 (AE1 or band 3) has a high prevalence in some tropical countries, particularly Thailand, Malaysia, the Philippines and Papua New Guinea (PNG). Here the disease is almost invariably recessive and can result from either homozygous or compound heterozygous SLC4A1 mutations. METHODS: We have collected and reviewed our own and published data on tropical dRTA to provide a comprehensive series of clinical and epidemiological studies in 78 patients. RESULTS: Eight responsible SLC4A1 mutations have been described so far, four of them affecting multiple unrelated families. With the exception of the mutation causing South-East Asian ovalocytosis (SAO), none of these mutations has been reported outside the tropics, where dRTA caused by SLC4A1 mutations is much rarer and almost always dominant, resulting from mutations that are quite different from those found in the tropics. SLC4A1 mutations, including those causing dRTA, may cause morphological red cell changes, often with excess haemolysis. In dRTA, these red cell changes are usually clinically recessive and not present in heterozygotes. The high tropical prevalence of dRTA caused by SLC4A1 mutations is currently unexplained. CONCLUSION: A hypothesis suggesting that changes in red cell metabolism caused by these mutations might protect against malaria is put forward to explain the phenomenon, and a possible mechanism for this effect is proposed.

Features of the metabolic syndrome after childhood craniopharyngioma.

Obesity and multiple pituitary hormone deficiency are common complications after surgery for childhood craniopharyngioma. We hypothesized that post craniopharyngioma surgery, children are at high risk for the metabolic syndrome, including insulin resistance due to excess weight gain and GH deficiency. This study characterized body composition (anthropometry and dual energy x-ray absorptiometry) and metabolic outcomes in 15 children (10 males and 5 females; age, 12.2 yr; range, 7.2-18.5 yr) after surgical removal of craniopharyngioma. In 9 subjects, outcomes were compared with those of healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Insulin sensitivity was measured by 40-min iv glucose tolerance test. Seventy-three percent of subjects were overweight or obese. Sixty-six percent had normal growth velocity without GH treatment. Subjects had increased abdominal adiposity (P = 0.008) compared with controls. However, there was no significant difference in total body fat. Subjects had higher fasting triglycerides (P = 0.02) and lower high density lipoprotein cholesterol to total cholesterol ratio (P = 0.015). Insulin sensitivity was equally reduced for subjects and controls (P = 0.86). After craniopharyngioma removal, patients had more features of the metabolic syndrome compared with controls. This could be a result of hypothalamic damage causing obesity and GH deficiency. Further studies exploring predictors of the metabolic syndrome after craniopharyngioma surgery are required.

Type 2 diabetes mellitus in Papua New Guinea--an historical perspective.

Type 2 diabetes mellitus is an increasing problem in Papua New Guinea (PNG). Five dominant themes emerge from the literature on diabetes in PNG: 1) The concept of the 'thrifty genotype' predisposing Papua New Guineans, like many other traditional populations, to type 2 diabetes, 2) Some coastal ethnic groups (particularly with Wanigelans and Tolais) appear to be more predisposed than others, 3) Prevalence of type 2 diabetes markedly rises with urbanization and adoption of a more western lifestyle, 4) Morbidity and mortality associated with the disease is high, and 5) Type 2 diabetes is overwhelmingly the most common type, with other types being rare. The literature is reviewed within the framework of these themes.

Type 1 diabetes mellitus in children in Papua New Guinea.

Anecdotal and published information suggest a low incidence and prevalence of type 1 diabetes in Papua New Guinea (PNG). Incidence and prevalence were followed prospectively from July 1996, using the PNG Paediatric Surveillance Unit (PSU). No children were receiving insulin in Papua New Guinea at the start of the period. Over the next 4.5 years, 8 cases were reported--an annual incidence of 0.08/100,000 children aged < 15 years and a prevalence of 0.28/100,000 aged < 15 years. These figures are as low as any reported elsewhere. Three cases were from the small expatriate population. All cases in Melanesian children posed significant management problems, with two children dying during the study period.

A survey of diabetes services in hospitals in Papua New Guinea.

AIM: To determine the number and distribution of diabetic persons in Papua New Guinea (PNG), and to document available services. METHODS: Survey of the 19 hospitals thought to be the most significant centres for care of diabetes. RESULTS: 16 hospitals were successfully surveyed. Type 1 diabetes is very rare, with 18 known cases in the country (6 less than 15 years old). Known type 2 cases totalled around 4600 with almost all cases in coastal centres, particularly Port Moresby, East New Britain and Manus. There were very few cases in the highlands. Insulin is generally available, along with oral hypoglycaemic drugs. Testing for complications is very limited, and glycosylated haemoglobin (HbA1c) testing is available in only one centre. Only 3 trained diabetes educators are available in the country, with 1 dietitian and no specialist endocrinologists. CONCLUSIONS: The vast majority of persons with type 2 diabetes in PNG are undiagnosed and are not receiving treatment: based on the lower of two country prevalence estimates, less than 3% of the diabetic persons in the country are seen at health facilities. Services are limited, with only a handful of health professionals specially trained in diabetes. Expansion of services and awareness and prevention programs are urgently needed.

Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells.

We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to berestricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.

Infant feeding practices in Papua New Guinea.

Concern about a possibly increasing prevalence of bottle-feeding led in 1995 to an Infant Feeding Survey of 1822 mothers attending urban health facilities. Infant feeding practices including feeding of colostrum, exclusive breastfeeding, weaning practices and bottle-feeding were assessed. This revealed that 28.8% of mothers had not given colostrum to their babies, that 43.5% of 3-month-old babies were exclusively breastfed, and that solids were introduced before 4 months of age in over half of the study population. Bottle-feeding was used by 20% of the study population. Feeding practices differed in women of Highlands and of Coastal origin. The findings emphasize the need to strengthen health education programmes which take into account the mothers' different cultural backgrounds. The issue of breast-feeding by mothers in paid employment needs to be addressed.

PIP: Recognizing the many benefits of breast-feeding, the government of Papua New Guinea (PNG) legislated to protect the practice 4 years before the introduction of the World Health Organization Code of Marketing restricting access to bottle feeding supplies. While exclusive breast-feeding for 4-6 months is recommended policy, it was noticed that many mothers introduce solids and fluids other than breast milk much earlier. In 1995, the Pediatric Society of PNG conducted a feeding survey to assess the prevalence of bottle feeding and review the effects of the imposed legislation. Infant feeding practices, including the feeding of colostrum, exclusive breast-feeding, weaning practices, and bottle feeding were assessed among 1822 mothers of children under age 2 years attending urban health facilities. 28.8% of the mothers had not given colostrum to their babies, 43.5% of 3-month old babies were exclusively breast-fed, and solids were introduced before age 4 months in more than half of the study population. 20% of the study population bottle fed. The prevalence of exclusive breast-feeding among employed Highlands women was lower than among employed Coastal women, but the difference was not statistically significant. Study findings point to the need to strengthen health education programs which take into account mothers' different cultural backgrounds. The issue of breast-feeding by mothers in paid employment also needs to be addressed.

Persistent diarrhoea in children admitted to Port Moresby General Hospital.

A retrospective study of the records of children admitted to Port Moresby General Hospital with diarrhoea during 1992 and 1993 was carried out to determine the morbidity, mortality and risk factors associated with persistent diarrhoea. 858 admissions of children under five years of age who had diarrhoea were identified from the ward admission registers, and case records for 724 were studied. Persistent diarrhoea occurred in 20%, and nearly half of these were in the 12-23 months age group. Children with persistent diarrhoea had a case fatality rate of 4.9%. Seasonality was similar for both persistent and non-persistent diarrhoea. In the crude analysis children of 12 months and older had a greater risk of developing persistent diarrhoea than those less than 12 months (odds ratio for children 12-23 months was 2.0 and for children 24-59 months 1.7; confidence intervals were 1.2-3.1 and 1.0-2.9 respectively); however, this difference was not found after logistic regression analysis. Poor nutritional status was a significant risk factor for persistent diarrhoea and remained so after controlling for confounding variables (odds ratio 2.7; confidence interval 1.8-4.0).

PIP: A retrospective review of the records of 724 children under 5 years of age admitted to Port Moresby General Hospital (Papua New Guinea) in 1992-93 with diarrhea was conducted, with emphasis on risk factors for persistent diarrhea. These cases represented 84% of total under-5 diarrhea admissions during the study period. Of the 720 children for which the duration of diarrhea was recorded, 144 (20%) had persistent diarrhea lasting 14 or more days. 49% of persistent diarrhea cases involved children 12-23 months of age; the largest proportion (40%) of short-term diarrhea cases occurred in infants 0-11 months old. Watery diarrhea, vomiting, cough, and fever were the most common presenting symptoms for diarrhea and acute respiratory tract infection was the most frequent cause of co-morbidity. Seasonal peaks in incidence occurred in May-July and November-January. After adjustment for dehydration-related weight loss, 42% of children with diarrhea were classified as malnourished. The case fatality rate was 4.9% for persistent diarrhea and 3.6% for non-persistent cases. In the univariate analysis, age and nutritional status were the only significant risk factors for persistent diarrhea; sex, past hospital admission, and co-morbidity were only weakly associated with persistent diarrhea. In the logistic regression analysis, only malnutrition remained a significant risk factor (odds ratio, 2.7; 95% confidence interval, 1.8-4.0). It is speculated that malnutrition associated with weaning accounts for the high rate of persistent diarrhea among children 12-23 months of age.

Body-composition assessment by dual-energy x-ray absorptiometry in subjects aged 4-26 y.

This cross-sectional study describes the body composition of 265 normal subjects (137 males and 128 females) aged 4-26 y determined by dual-energy x-ray absorptiometry (DXA). Lean tissue mass (LTM) and bone mineral content (BMC) increased with age in females until 13.4 and 15.7 y, respectively, and in males until 16.6 and 17.4 y, respectively. A strong relation between LTM and BMC was found for each sex (r = 0.98, P = 0.0001 for males; r = 0.98, P = 0.0001 for females). DXA percent body fat (%BFDXA) increased with age in females (r = 0.52, P < 0.001) but not in males and was higher in females than in males at all ages. Trunk to leg fat ratio (TLFR) was calculated as DXA trunk fat/leg fat. In post-pubertal age the TLFR was higher in males than in females (1.01 +/- 0.23 and 0.75 +/- 0.16, P = 0.001), but there was no sex difference in younger children. DXA weight underestimated scale weight by a mean of 0.83 kg. %BFDXA correlated with %BF by skinfold thickness measurement with good agreement for males but overestimated %BF by skinfold thickness for females. These normative data for body composition demonstrate significant sex differences in all body compartments after the pubertal years.

Bone mineral density of total body, spine, and femoral neck in children and young adults: a cross-sectional and longitudinal study.

Bone mineral density (BMD) of total body (TBMD), lumbar spine (L2-4), and femoral neck was measured in 266 normal subjects (136 males) aged 4-27 years (mean 13 years) using dual-energy x-ray absorptiometry (DXA). BMD of all sites increased significantly with age until 17.5 years in males and 15.8 years in females, except for femoral neck BMD in females, which peaked at age 14.1 years. Males had higher peak TBMD, which was attributed to greater weight and lean tissue mass. In contrast, despite a later timing, peak L2-4 BMD in males was not different from that in females. Before peak BMD, weight was the best predictor of TBMD and L2-4 BMD in both sexes (r2 ranged from 0.77 to 0.88), whereas femoral neck BMD was predicted equally by height and weight. Longitudinal information collected from 53 (25 boys) of these children, aged 4-16.9 years, showed that the average annualized gain in TBMD was 0.047 g/cm2 for boys and 0.039 g/cm2 for girls. No significant difference in the association between age and BMD (slopes) was found between cross-sectional and longitudinal data for either sex. We conclude that the timing for peak BMD was consistent for total body, lumbar spine, and femoral neck for each sex. The earlier peak BMD in females is most likely related to earlier puberty. The cross-sectional normative data of this study are useful in serving as a standard for serial assessment in health and disease states.

Changes in body composition and bone density after discontinuation of growth hormone therapy in adolescence: an interim report.

Growth hormone deficiency (GHD) in adults and children is associated with decreased lean tissue mass (LTM), increased fat mass and reduced bone mineral density (BMD). The changes in BMD and body composition, 6 and 12 months after ceasing GH treatment, were assessed using dual-energy X-ray absorptiometry in eight patients with GHD (age range, 13.8-17.5 years). Seven age-matched normal subjects who had completed growth were assessed at 0 and 12 months. Total body BMD was low at baseline (p < 0.05) in patients with GHD compared with the predicted values based on sex-specific regression equations, with height, weight and age taken into account. Total body, lumbar spine and femoral neck BMD increased in the patients and controls at 12 months. LTM decreased significantly by a mean of 1.37 kg in the patients with GHD at 12 months whereas there was a non-significant increase in LTM in the control group. The percentage of body fat increased in all patients with GHD at 6 and 12 months, from 27.2 +/- 11% (mean +/- SD) at baseline to 32 +/- 9.9% at 12 months (p = 0.009). There was no significant increase in mean percentage body fat in the control group. The ratio of android (trunk):gynoid (legs) fat was calculated using default settings of dual-energy X-ray absorptiometry. The mean android:gynoid fat ratio increased, though non-significantly, in patients with GHD at 12 months, with 6 of 7 showing an increase; no change was observed in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of growth hormone treatment for short stature on calcium homeostasis, bone mineralisation, and body composition.

We investigated the effect of growth hormone (GH) treatment on mineral and vitamin D homeostasis, bone mineralisation, and body composition in short-statured children without GH deficiency (GHD). 11 children received GH (0.50 +/- 0.08 IU/kg/week) for 24 weeks. 1,25-Dihydroxyvitamin D3 levels (mean +/- SD in pmol/l) rose from a baseline of 73.7 +/- 39.2 to 114.0 +/- 32.7 at 8 weeks (p < 0.05) and 111.9 +/- 39.7 at 24 weeks (p < 0.01). Body composition evaluation using dual-energy X-ray absorptiometry revealed increased lean tissue mass and a reduction in fat tissue. As a percentage of total body mass, fat decreased from 19.0 +/- 11.8% at baseline to 17.3 +/- 11.5% at 8 weeks (p < 0.005) and 16.8 +/- 11.5% at 24 weeks (p < 0.05). L2-L4 bone mineral density was 0.637 +/- 0.155 g/cm2 at baseline and 0.666 +/- 0.160 g/cm2 at 24 weeks (NS). We conclude that recombinant human GH treatment of short children without GHD has significant effects on vitamin D homeostasis and body composition.

Renal effects of growth hormone. II. Electrolyte homeostasis and body composition.

Growth hormone (GH), either directly or through insulin-like growth factor-1 (IGF-1), has a wide spectrum of physiological and renal effects. This review concentrates on the effects of GH (derived from either pituitary or recombinant technology) and IGF-1 in three main areas: (1) sodium and water homeostasis; (2) calcium and phosphate balance, bone density and interactions with mineral regulating hormones; (3) fat and lean body mass. Observations of physiological changes in states of GH deficiency and excess in humans and animal models are presented. The lack of long-term toxicological data indicates that GH treatment for short stature in non-GH deficient children, with or without renal disease, should proceed with caution.

Renal effects of growth hormone. I. Renal function and kidney growth.

Growth hormone (GH) affects renal function and kidney growth. Pituitary-derived or recombinant human GH (rhGH), acting via insulin-like growth factor-1 (IGF-1), increases glomerular filtration rate (GFR) and renal plasma flow (RPF) in GH-deficient as well as in normal adults. Furthermore, GFR and RPF are low in hypopituitarism and elevated in acromegaly. These effects of GH on GFR and RPF have not been demonstrated in moderate renal insufficiency. IGF-1 is implicated in compensatory renal hypertrophy. Markedly elevated levels of serum GH accelerate glomerular sclerosis in rodents, although the significance of these findings for GH treatment in humans is uncertain. rhGH therapy offers great promise to children with short stature from various aetiologies. Preliminary reports on the use of rhGH in children with renal disease and after renal transplantation have not shown any consistent change in kidney function, although follow-up times are short. The long-term impact of rhGH therapy on kidney function in short children needs further evaluation.

Ioxaglate in paediatric angiocardiography.

It is generally agreed that low osmolar contrast media are better tolerated than conventional media. This study examined both tolerance and image quality of ioxaglate in a group of paediatric patients undergoing angiocardiography for congenital heart disease. A consecutive series of 50 patients (mean age 5.47 years; range 4 days-14 years) were examined. The mean dose of ioxaglate administered per patient was 2.93 mL/kg. In general, ioxaglate was well tolerated. Three patients became febrile and another developed eosinophilia. Serum creatinine rose by a mean of 10 mumol/L. Significant renal dysfunction occurred in 12 patients with an increase in creatinine of 20-30 mumol/L. In no patient, however, were these effects a significant clinical problem. Diagnostic image quality was generally considered to be good with both cine-angiography and digital subtraction angiographic techniques.