Reviews
Prevention of Diabetes in Children
Louis Pasteur in his address in 1884 remarked: "When mediating over a disease, I never think of finding a remedy for it, but instead a means of preventing it"[1]. It still remains an indisputable fact that ultimate goal in treatment of any disease including diabetes is its prevention. The incidence of Type 1 diabetes differs in different parts of the world. The highest rate of diabetes is found in Finland and Scandinavia followed by USA [1]. The prevalence of Type1 diabetes in USA is 2-3/1000 with annual incidence of approximately 15/100000 children, or more than 12000 children per year. Thus this high rate of incidence of Type 1 diabetes contributes greatly to overall morbidity and mortality. A number of clinical studies were conducted to identify population with high disease risk and thus helping in its prevention [2]. This review will focus on different clinical trials carried out in last few years and the complications of intensive therapy. IDDM Prevention Trials DTP-1 TRIALS A clinical trial known as Diabetic Prevention Trial (DTP-1) was initiated in 1994,in USA with the aim of determining whether antigen-based therapies using insulin would prevent or delay the onset of diabetes in the at-risk relatives [1]. The pilot studies conducted giving insulin therapy to high-risk relatives, as prophylactic parental insulin injection showed promising results[3]. In the DTP-1 trial, low dose parental insulin therapy (annual iv infusion followed by daily sc injections) were administered to a high-risk group of relatives and was compared with untreated closely monitored group [1] [3]. Another double blind trial between two groups (oral insulin vs. placebo) was carried out in relatives with intermediate risk (25-50% over 5 years). More than 60,000 relatives were screened with over 275 (target 360) randomized to high-risk arm and 223(target 499) of intermediate risk group. The results of this trial are still awaited [1]. A clinical trial was launched in Pittsburg to study the effect of decreased mental efficiency caused by hypoglycemia (60mg/dl) [4]. The study was carried out between two groups. One group in which insulin injections were administered twice daily and other control group without any therapy. The conclusion drawn from this trial indicated that a dose as small as 0.25u/kg/day of ultralente insulin produced significant hypoglycemia which affected their performance in school [2][4]. DCCT (Diabetic Control and Complications Trials) In Diabetes Control and its Complications Trial intensive insulin therapy was used in the management of Type 1 diabetes. The results of this trial indicated that the intensive regime not only effectively delays the onset but also slows the progression of diabetic retinopathy, nephropathy and neuropathy in patients with Type 1 diabetes[5][6][7]. As only about 14% of the subjects when enrolled in the DCCT were between the age group 13 and 17 years, to study the effect of this therapy on children separate subset analyses were carried out in 195 patients who were within this age group limit (125 primary prevention and 70 secondary intervention patients)[7]. The results obtained from these analyses were compared with those of adults who were enrolled into the trial. From this study it was observed that intensive therapy improved nerve conduction velocity and lowered fasting low-density lipoprotein in the adolescent in this age group [7]. But, even though the adolescent in the DCCT trial who were administered intensive therapy had higher HbAIC levels, their risk of severe hypoglycemia was substantially greater than in adults (86 vs 56/100 patient years) [7]. Another study was carried out to examine whether DCCT could be implemented in adoloscents. Seventy five patients who are enrolled in the study completed one year of follow-up. 50 patients were given MDI(Multiple Dose Insulin) and 25 CSII(Continuous Sucutaneous Insulin Infusion). Hb A1c levels improved in both the groups after a period of one year. In MDI group (from 8.8 + 1.6 to 8.4 + 1.3%) and in CSII group (8.4+ 0.9 to 7.5 + 0.9%). Despite lower HbA1c levels, the rate of severe hypoglyceamic events was 50% lower with CSII than MDI(76 vs 134 events /100 patient years)[7]. The final outcome of the study showed that CSII offers a treatment option that can lead to improve control and lower the risk of severe hypoglycemia in comparison to MDI[7]. Current Trials TRIGR (Trial to reduce Diabetes in Genetically at Risk) A study was conducted in Finland to test whether strict avoidence of complex protein diet, such as common cow-milk based formulas in the first six months of life, would prevent the development of diabetic auto immunity and/or overt disease in genetically susceptible new born infants [2]. In this randomised placebo-controlled prospective trial new born first-degree relatives with high genetic risks were subjected to a weaning diet of either standard formula or a hydrolysed casein formula. The preliminary results indicated significantly decreased auto antibodies in the group fed with hydrolysed formulas [2]. Although this study is safe it is difficult to implement. A large multicentre study is warranted to confirm whether avoidance of complex weaning diets, such as cow-milk formula, has an effect on the development of IDDM in humans. The other centers where such type of studies is carried out are The BABYDIAB (German multi center study investigating auto immunity in off spring of diabetic parents. DIPP (Finnish Type 1 diabetes reduction and prevention project), Diabetes auto immunity Study in the Young (DAISY) [1]. Nicotinamide trial DENNIS (Deutsche Nicotinamide Intervention Study) [2][9]: This study
involved high-risk group of young relatives was a small randomized
trial. The aim of this trial was to find out does oral nicotinamide
really helps in 80% reduction of IDDM incidence. ENDIT (European Nicotinamide Diabètes Intervention Trial) Comments The risk of intervention should be weighed clearly against the risks and discomfort of the treatment of diabetes as we approach the new millennium A lot needs to be learned about dosage of prevention therapies that are currently being investigated in both animal models and humans. One has to proceed with great care during primary or secondary intervention strategies in newborn and young. There is no doubt that further trials will be carried on in future. The results of these trials would some day pave the path for safe prevention of Type 1 diabetes. References
|
 |
