The changing model of insulin use in type 2 diabetes. Techniques, tactics for getting to goal.

Type 2 diabetes is by far the predominant type of diabetes in the United States. Lifestyle changes can be effective in controlling blood glucose levels in many patients with early type 2 diabetes. However, as the disease evolves and slowly progresses, its successful treatment can move beyond diet and exercise to oral antidiabetic agents and later to the addition of insulin to oral therapy. Both physicians and patients may be hesitant to start insulin treatment, which can be complex and need ongoing adjustment. Here, Dr Cooppan describes the indications for insulin use in type 2 diabetes, outlines the insulin analogue therapies available, and explains the latest in best management strategies for using insulin and getting to goal.

Epidemiology and control of schistosomiasis mansoni in communities living on the Cuando River floodplain of East Caprivi, Namibia.

The Cuando River area of eastern Caprivi, Namibia, is highly endemic for Schistosoma mansoni whereas S. haematobium transmission, due to the scarcity of its intermediate host snail, Bulinus africanus, does not occur. Chemotherapy (6-monthly blanket treatments with praziquantel) combined with focal mollusciciding (monthly application of niclosamide) was used in a project in the area to control the disease. Although as many adults and pre-school children as possible were tested and treated, the project concentrated largely on school-age children. It took 3 years for prevalence to decline from > 80% to 20% because of a lack of proper sanitary facilities and piped water supplies and high rates of absenteeism and re-infection. However, intensity of infection decreased more rapidly, from an arithmetic mean of > 200 to < 5 eggs/g faeces. Hepatomegaly was common among school children when the project started but could be seen in only a small percentage of them after 3 years of control. Neither the bovine schistosome, S. mattheei, nor the lechwe schistosomes, S. margrebowiei and S. leiperi, were observed in the excreta of humans living in the area.

Transfer of DDT used in malaria control to infants via breast milk.

The transfer of p,p'-DDT (1,1,1-tricholoro-2,2-bis(4-chlorophenyl)ethane) and its metabolites to infants via breast-feeding was studied in an area of KwaZulu, South Africa, where DDT is used to interrupt malaria transmission. Samples of whole blood were collected from 23 infants, together with samples of breast milk from their respective mothers. The mean sigma DDT (total DDT) in the whole blood was 127.03 micrograms.l-1 and that in the breast milk, 15.06 mg.kg-1 (milk fat). The % DDT (% DDT of sigma DDT) was significantly higher in the infant blood than in the breast milk (P less than 0.05). A multiplicative regression analysis indicated that sigma DDT increased significantly (P less than 0.01) in infant whole blood with infant age. Multiple regression showed that 70.0% of the variation in sigma DDT was due to the variation in parity of the mother, age of the infant, and the sigma DDT in breast milk. These variables accounted also for 76.3% of the variation in p,p'-DDE but only for 38.2% of that in p,p'-DDT. Organochlorines were therefore largely transferred to the infant from the mother, with DDT in the environment playing a secondary role.

Transfer of DDT used in malaria control to infants via breast milk

The transfer of p,p'-DDT (1,1,1-tricholoro-2,2-bis(4-chlorophenyl)ethane) and its metabolites to infants via breast-feeding was studied in an area of KwaZulu, South Africa, where DDT is used to interrupt malaria transmission. Samples of whole blood were collected from 23 infants, together with samples of breast milk from their respective mothers. The mean sigma DDT (total DDT) in the whole blood was 127.03 micrograms.l-1 and that in the breast milk, 15.06 mg.kg-1 (milk fat). The % DDT (% DDT of sigma DDT) was significantly higher in the infant blood than in the breast milk (P less than 0.05). A multiplicative regression analysis indicated that sigma DDT increased significantly (P less than 0.01) in infant whole blood with infant age. Multiple regression showed that 70.0% of the variation in sigma DDT was due to the variation in parity of the mother, age of the infant, and the sigma DDT in breast milk. These variables accounted also for 76.3% of the variation in p,p'-DDE but only for 38.2% of that in p,p'-DDT. Organochlorines were therefore largely transferred to the infant from the mother, with DDT in the environment playing a secondary role

The effects of parasite infections on cognitive processes in children.

Two studies were carried out in the Nyuswa area of Natal to investigate the effects of parasitic infection on cognitive function in children. In the first study, children infected with intestinal helminths were given tests of information processing and perceptual speed before and after treatment with a single 500 mg dose of Mebendazole. The pattern of results was consistent with the hypothesis that parasitic infections combine with nutritional deficits to impair the efficiency of cognitive processes. There was, however, some confounding of variables, and the single drug treatment reduced but did not eliminate the parasites. The second study removed the confounding effects due to age and nutrition and employed a more comprehensive drug-treatment programme. A memory task and a test of sustained attention were administered. Poor performance on the attention task showed a significant association with parasite status, but no association was observed with educational attainment or memory function. The study also examined various ways of assessing parasite load, and an index weighted for estimated pathogenicity was found to give the best estimate. The results provide evidence of the effects of parasitic infection on attentional processes.

Malaria control and levels of DDT in serum of two populations in Kwazulu.

Concentrations of p,p'-DDT, p,p'-DDE, and p,p'-DDD were determined in serum of members of households of two different areas of KwaZulu. Annual intradomiciliary application of DDT is used for the interruption of malaria transmission in one area (the exposed group) while the other served as the control. Demographic differences between the two groups resulted in significantly more females in the control group. The two groups were comparable with respect to age. Serum from household members living in DDT-treated dwellings had significantly higher (p less than .005) levels of sigma DDT and metabolites (mean sigma DDT 140.9 micrograms/l) than those from the control area (mean sigma DDT 6.04 micrograms/l). Percentage DDT was also significantly higher (p less than .05) in the exposed group (28.9%) than the control group (8.3%). sigma DDT for the 3-10 yr age interval (168.6 micrograms/l) was significantly higher (p less than .05) than the 20-29 (60.5 micrograms/l) and 30-39 (84.2 micrograms/l) yr age intervals. There seemed to be two groups with regard to accumulation and elimination. The age group 3-29 appeared to be eliminating DDT, most likely accumulated from contaminated breast milk, faster than they accumulated it. From around 29 yr of age accumulation predominated as the levels increased with age. Regression analysis suggested pharmacokinetic differences for DDE and DDT between the two groups. Liver function parameters between the two groups only differed significantly for gamma-glutamyl transferase (gamma GT) (p less than .005), but the influence of difference in alcohol consumption, which was significantly higher in the exposed group (p less than .0001), offered a better explanation. Those of the exposed group that consumed alcohol had a significantly higher (p less than .05) mean gamma GT level (41.5 IU/l) than those that did not (20.2 IU/l), but were not significantly different for sigma DDT (p greater than .05). The safety of DDT used in malaria control for subjects aged 3 and older was confirmed by the levels of DDT in serum when compared with other studies, which showed lack of any negative effects associated with these levels in adults, and an apparently normal liver function in the exposed and control groups.

Serum levels of DDT and liver function of malaria control personnel.

The levels of DDT and metabolites in serum of 23 applicators involved in malaria control operations in Natal were determined using gas chromatography with electron capture detection. The mean levels (microgram/l, ppb) were 61.7 DDT, 129.3 DDE, 11.0 DDD and 202.0 sigma DDT. Percentage DDT was 33.4%. These levels were higher than for an age matched sample of the general population in KwaZulu, who are protected by DDT against malaria. Percentage DDT correlated negatively with age (P less than 0.05) for the applicators, suggesting a change in pharmacodynamics with age. Mean serum albumin, alkaline phosphatase, aspartate transferase and gamma-glutamyltransferase (GGT) levels did not differ significantly from an age-matched control group, but the mean GGT value for the applicators was higher than the maximum of the laboratory normal range. Although not clinically significant, the alanine transferase was significantly higher in the applicators than in the control group. These higher levels suggest a possible risk to the health of the sprayers, but uncertainties remain.

Factors affecting levels of DDT and metabolites in human breast milk from Kwazulu.

Concentrations of p,p'-DDT, p,p'-DDE, and p,p'-DDD have been determined in breast milk of mothers residing in two different areas of KwaZulu. Annual intradomiciliary application of DDT was used for the interruption of malaria transmission in one area, while the other served as the control. Milk from mothers living in DDT-treated dwellings had significantly higher mean levels of DDT and metabolites (mean sigma DDT 15.83 mg kg-1 in milk fat) than those from the control area (0.69 mg kg-1). The highest recorded sigma DDT value was 59.3 mg kg-1 (milk fat). Primiparous mothers from the malarious area had significantly more sigma DDT and metabolites (sigma DDT 24.82 mg kg-1) than multiparous mothers from the same area (mean 12.21 mg kg-1). Parity was the best predictor of DDT in breast milk of the exposed group. The percentage DDT and the sigma DDT increased significantly with an increase in parity. The same, but not significant, trend was also found for the control group. It was hypothesized that the increase in percentage DDT that occurred with higher parities was due to the uptake of DDT and elimination via milk. This process was faster than the uptake and endogenous formation of DDE. Designing predictive models using multiple regression was not very successful. The recorded levels do not represent an appreciable health risk to the mothers. From the literature it was deduced that at the recorded levels, a well-founded risk to the infants, particularly the firstborns, exists in sprayed areas.

Levels of DDT and metabolites in breast milk from Kwa-Zulu mothers after DDT application for malaria control.

Concentrations of DDT, DDE and DDD were determined in the breast milk of Kwa-Zulu mothers residing in two different areas--with and without annual intra-domiciliary applications of DDT for the interruption of malaria transmission (exposed and control groups, respectively). While no significant change in levels with time was found in the control group, both DDT and DDE in breast milk of the exposed group increased after DDT application and this continued for three more months, after which it did not decrease appreciably. Percentage DDT increased from 42.57% (sigma DDT = 12.21 mg/kg milk fat) before spraying to 50.87% (sigma DDT = 13.79 mg/kg milk fat) following DDT application. At 6 and 9 months after the application it was 45.85% (sigma DDT = 19.49 mg/kg milk fat) and 43.27% (sigma DDT = 18.34 mg/kg milk fat), respectively. These results suggest a risk to the health of the infants in the exposed group.

Levels of DDT and metabolites in breast milk from Kwa-Zulu mothers after DDT application for malaria control

Concentrations of DDT, DDE and DDD were determined in the breast milk of Kwa-Zulu mothers residing in two different areas--with and without annual intra-domiciliary applications of DDT for the interruption of malaria transmission (exposed and control groups, respectively). While no significant change in levels with time was found in the control group, both DDT and DDE in breast milk of the exposed group increased after DDT application and this continued for three more months, after which it did not decrease appreciably. Percentage DDT increased from 42.57% (sigma DDT = 12.21 mg/kg milk fat) before spraying to 50.87% (sigma DDT = 13.79 mg/kg milk fat) following DDT application. At 6 and 9 months after the application it was 45.85% (sigma DDT = 19.49 mg/kg milk fat) and 43.27% (sigma DDT = 18.34 mg/kg milk fat), respectively. These results suggest a risk to the health of the infants in the exposed group

Urinalysis reagent strips in the screening of children for urinary schistosomiasis in the RSA.

The use of urinalysis reagent strips (Labstix; Ames) in screening for Schistosoma haematobium infection in various schistosomiasis-endemic areas of the RSA was assessed in 941 children. Sensitivity, specificity, false-positive and false-negative rates and the positive predictive value for haematuria and proteinuria were calculated. Both haematuria and proteinuria were positively correlated with the presence of S. haematobium eggs in the urine. Intensity of infection correlated positively with the degree of haematuria and proteinuria (P less than 0.001). The presence and intensity of S. haematobium infection were more closely related to the presence and degree of haematuria than to proteinuria. Screening for haematuria alone enabled 83.1% of S. haematobium-positive and 89.7% of negative subjects to be detected accurately. The false-positive rate was 2.7%. It was found that a single parameter, haematuria, could be used to identify infected children in endemic areas. It was also found to be possible to use the reagent strips to select out S. haematobium-infected children with egg counts greater than 200 ova/10 ml urine. The simple model developed allows rapid identification of moderately to heavily infected children and can be used by paramedical staff in field situations.

Determining the most appropriate treatment for patients with non-insulin-dependent diabetes mellitus.

Today it is possible, with the available treatment armamentarium, for a physician to rationally choose a strategy to be customized to patients with type II diabetes. The keystone of treatment is a good nutritional plan that provides for proper nutrition as well as appropriate weight loss. Exercise is also a useful adjunct. When diet therapy is unsuccessful, the use of oral sulfonylureas may be indicated. These agents have been shown to stimulate insulin release, to reduce hepatic glucose output, to potentiate insulin action in a postreceptor mechanism, and to have a modest effect in increasing insulin receptors. The first-generation compounds have a 70% success rate within the first 5 years after initiating therapy. However, these agents can have undesirable side effects. The second-generation agents, such as glipizide, offer the advantages of high efficacy, inactive metabolites, nonionic binding, and low reported alcohol flushing. Many patients who fail on first-generation agents may respond to second-generation drugs. Insulin therapy can be used if the patient fails on an oral agent.

Morbidity from urinary schistosomiasis in relation to intensity of infection in the Natal Province of South Africa.

Morbidity from urinary schistosomiasis was assessed on clinical, radiological, parasitologic and biochemical evidence in 510 schoolchildren living in a Schistosoma haematobium endemic area. The results were viewed against the background of the prevalence and intensity of infection in the subjects. Clinical morbidity correlated well with the intensity of infection, the latter in turn being influenced by factors such as water contact pattern, sex and water source. A surprisingly high prevalence (42%) of abnormalities was observed in the urinary tract of subjects, but no relationship could be demonstrated between the intensity of infection and structural damage to the urinary tract. Urographic changes were more severe in the 11-15 year age group than in the 6-10 year group. Significant rectal involvement (76%) in S. haematobium-infected subjects was regarded as a reflection of the heavy worm burdens borne by these children. The morbidity described in this study indicates a definite degree of pathology in the infected children but the impression was that they suffered only mild disability. However, given the structural lesions seen on urography and the limited sensitivity of the biochemical tests used for the assessment of renal function, renal pathology cannot be ruled out. Further studies on the renal status of these subjects are essential.

Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver.

In an investigation to determine the influence of sampling variability on the diagnostic yield of liver biopsy, 3 consecutive samples were obtained from each of 75 patients by redirecting the biopsy needle through a single entry site. In 14.7% of patients all 3 specimens were normal, and in 36% there were similar abnormalities in all 3 specimens. In the other patients, sampling variability between specimens was present. In those patients with cirrhosis, hepatocellular carcinoma, metastatic carcinoma, or hepatic granulomas the histological abnormality was present in all 3 biopsy specimens in only 50%, 54.5%, 50%, and 18.8% of patients, respectively. No complications were recorded. These findings show that important pathology can be overlooked if only a single biopsy specimen is taken, and that the method of obtaining 3 consecutive specimens improves the diagnostic yield of liver biopsy without an associated increase in complications.