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临床试验/NCT05361148
NCT05361148已完成不适用

Long-term Health After Severe Acute Malnutrition in Children and Adults: the Role of the Pancreas

London School of Hygiene and Tropical Medicine4 个研究点 分布在 4 个国家目标入组 2,305 人开始时间: 2021年1月12日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
2,305
试验地点
4
主要终点
Pancreas endocrine function

研究概览

简要总结

Whilst there is an increasing prevalence of overweight and obesity worldwide, malnutrition remains common. In addition, malnutrition, overweight, and infections often interact. The consequences of malnutrition after birth are little studied. Severe acute malnutrition in childhood remains common in Africa and Asia and many adult patients with tuberculosis or HIV, diseases which are common in Africa and Asia, may become malnourished. The investigators are interested in diabetes, which in Africa and Asia affects people at younger age and lower weight than in Europe. There is evidence that severe postnatal malnutrition increases the risk of later diabetes but the evidence is piecemeal and there is little information as to the mechanisms involved. It is thus difficult to determine what treatments or preventative strategies are appropriate.

The investigators wish to focus on the pancreas which is a key organ in digestion and metabolic processes, especially in relation to diabetes. They will investigate pancreas size, microscopic structure, hormone and digestive enzyme production, and the body's response to these hormones among groups of people in Tanzania, Zambia, India and the Philippines. These groups have participated in the research team's previous studies of malnutrition and were malnourished before birth, as children, or as adults. They now live in places with a wide range of access to foods high in fat and sugar which could affect their risk of diabetes. The investigators will compare their pancreas function to that of never-malnourished controls at each site. The investigators will use advanced statistical methods to understand the links between early malnutrition and later diabetes, taking into account the factors often associated with diabetes such as age, current overweight and infection.

Even if the investigators find no important link between early malnutrition and later diabetes, the research will lead to improved understanding of the long-term consequences of malnutrition and the presentation and underlying metabolism of diabetes in Africa and Asia. Thus, the project will lead to improved health care for both malnourished and diabetic people.

详细描述

Prenatal growth retardation is associated with increased risk of adult chronic non-communicable diseases (NCDs) including diabetes. However, there is limited information regarding how postnatal malnutrition, in childhood or adulthood, affects these risks. The question of long-term effects of postnatal malnutrition is of increasing importance, because, with improved care, more children survive severe acute malnutrition and, amongst adults, drug treatments for infections, e.g. HIV and tuberculosis which frequently cause or are associated with malnutrition (MALN), have improved patient survival. Our project will focus on the role of the pancreas in the long-term consequences of MALN since both its endocrine and exocrine functions are critical for nutrition and NCDs. There is evidence that pancreatic functions may not recover fully after childhood or adult MALN and that the phenotype of diabetes in countries with prevalent MALN differs from that in high-income countries.

Overall hypothesis:

Severe malnutrition (MALN) at any age has medium- and long-term detrimental effects on endocrine and exocrine pancreatic function and structure.

Study design and population: Cross-sectional observational study recruiting a total of 3700 participants from previous/ongoing observational cohorts in: Zambia (1 adult (N=300) and 1 adolescent cohort (N=180)), Tanzania (1 adult cohort (N=1400)), Philippines (2 adult cohorts N=600/N=420), India (1 adolescent low birth weight cohort N=800))

Specific objective 1: To determine if MALN earlier in life is associated with abnormalities of pancreas structure and function.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Cross Sectional

入排标准

年龄范围
8 Years 至 90 Years(Child, Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • member of one of the 6 included cohorts
  • informed consent (for children, informed assent and consent of guardian)

排除标准

  • lack of consent
  • pregnant women and chidlren will be excluded from CT scans and interavenous glucose tolerance tests

结局指标

主要结局

Pancreas endocrine function

时间窗: 1 year

Mathematical modelling of blood glucose, insulin and C-peptide at 3 (for children) or 7 (for adults) times during a 120 minute oral glucose tolerance test (OGTT) to determine first and second phase insulin release and insulin resistance

Pancreas exocrine function

时间窗: 1 year

faecal elastase and plasma lipase

次要结局

  • pancreatic calcification(1 year)
  • Proinsulin(1 year)
  • Pancreas size and structure(1 year)
  • insulin production and insulin resistance (in-depth study in a subset)(1 year)
  • abnormal prior pro-insulin/insulin ratio and diabetes (subset)(1 year)
  • Hemoglobin A1c(1 year)
  • gastrointestinal contribution to glucose metabolism and diabetes(1 year)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (4)

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