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Researchers identify an important adipocyte hormone
SCIENCE AND MEDICINE
Researchers identify an important adipocyte hormone diponectin, a hormone produced by adipocytes, could be a crucial link between obesity and insulin resistance, suggest two studies published this week. Takashi Kadowaki (University of Tokyo, Japan) and colleagues have shown that reduced expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. In one experiment, db/db mice, which are a model of type 2 diabetes, were found to be deficient in endogenously produced adiponectin compared with wild-type mice. Replacement therapy with purified adiponectin partially restored concentrations of the hormone and ameliorated hyperglycaemia and hyperinsulinaemia. The investigators also found a close relation between adiponectin and leptin, because insulin resistance in mice that lack adipose tissue was reversed by a combination of leptin and adiponectin, but only partially by either protein alone (Nat Med 2001; 7: 941–46). In a separate study, Philipp Scherer (Albert Einstein College of Medicine, Bronx, NY, USA) and co-
A
late that low serum adiponectin levels before TZDs administration may serve as a sensitive marker to predict responsiveness to TZDs”, says Kadowaki. Evan Rosen (Dana-Farber Cancer Institute, Boston, MA, USA) notes that although there are likely to be several links between obesity and diabetes, decreased adiponectin secretion by fat cells in obesity looks as good as any other proposition to date. “The data appear convincing that it can reduce bodyweight, glucose, and insulin levels in obese diabetic mice”, he says. Although adiponectin is a protein, which makes it a less attractive candidate for use in human beings than other oral drugs in development, he stresses that a previous study (Proc Natl Acad Sci 2001; 98: 2005–10) has shown adiponectin to have one very special advantage over other potential drugs. “It causes weight loss. Almost all other antidiabetic drugs, including insulin, cause incidental weight gain, making them problematic for people who are overweight to begin with”, he says.
workers revealed that a single injection of adiponectin triggers a transient decrease in basal glucose concentrations in normal mice, and transiently abolishes hyperglycaemia in ob/ob and non-obese diabetic mice. This effect is not associated with an increase in insulin concentrations, and the researchers conclude that adiponectin reduces insulin resistance (Nat Med 2001; 7: 947–52). Both groups are now focusing on identification of the adiponectin receptor. Further studies in Scherer’s laboratory include generation of mouse models with genetically altered concentrations of adiponectin. “Since this is a protein with therapeutic, potential, future challenges will also include the production and delivery of sufficient amounts into the bloodstream”, he says. Kadowaki’s group is also interested in the adiponectin pathway as a therapeutic target. “Thiazolidinedione derivatives (TZDs) such as rosiglitazone and pioglitazone are potent adiponectin secretagogues and this may account for their actions as insulin-sensitiser and antidiabetic drugs. We also specu-
Kathryn Senior
Psychiatric disorders still evident in Bosnian refugees early half of former Bosnian refugees who remained living in the conflict region still show symptoms of psychiatric disorders and disability 3 years after initial assessment, report US researchers this week. “These findings reveal the serious chronic mental health impact of mass violence. In particular, depression was unremitting, disabling, and potentially associated with premature death in the elderly”, says Richard Mollica, one of the investigators. Mollica (Harvard Program in Refugee Trauma, MA, USA) and colleagues have followed the mental health impact of the recent war in Bosnia on a camp of Bosnian refugees (534 adults) who had initially found asylum in Croatia in 1996 and who are now returning home or are being resettled elsewhere in Europe and the USA. In their initial study, they reported a high rate of disability associated with depression and post-traumatic stress disorder (PTSD) among the refugees (JAMA 1999; 282: 433–39). Mollica and colleagues assessed whether these relations have continued over time and are associated
390
with mortality and further emigration. They report that at follow-up, 376 (70·4%) refugees remained living in the Balkans, 39 (7·3%) had died, 114 (21·3%) had emigrated, and 5 (1%) were lost to follow-up.
Rights were not granted to include this image in electronic media. Please refer to the printed journal. AP
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Depression persists in Bosnian refugees
The investigators reinterviewed the refugees who had remained in the Balkans or the families of those who had died. 45% of the original respondents still had their psychiatric disorders. But only 16% of those who did not have symptoms of psychiatric disorder in 1996 had symptoms at follow-up. Refugees with depression had three times the risk of dying than those who were not depressed, but this relation was not significant after
adjustment for age, sex, and other factors. “The long-term impact of depression and PTSD on the development of cardiovascular disease and the potential for premature death in the elderly is a serious public health concern”, says Mollica. Refugees who emigrated were more traumatised, better educated, and had fewer health and mental-health problems than the majority who remained in the region (JAMA 2001; 286: 546–54). “These study results suggest the importance of early intervention in identifying and treating refugees with psychiatric disorders, especially depression”, says Mollica. Nathan Ford (Médecins Sans Frontières) agrees: “Mental health programmes should be seen as a core part of the emergency response to conflict, set up as early as possible during the emergency phase, because time is required to find and train local staff and understand the local context. It is vital to realise that an end to war does not mean an immediate return to normal life.” Minal Chande
THE LANCET • Vol 358 • August 4, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Researchers identify an important adipocyte hormone diponectin, a hormone produced by adipocytes, could be a crucial link between obesity and insulin resistance, suggest two studies published this week. Takashi Kadowaki (University of Tokyo, Japan) and colleagues have shown that reduced expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. In one experiment, db/db mice, which are a model of type 2 diabetes, were found to be deficient in endogenously produced adiponectin compared with wild-type mice. Replacement therapy with purified adiponectin partially restored concentrations of the hormone and ameliorated hyperglycaemia and hyperinsulinaemia. The investigators also found a close relation between adiponectin and leptin, because insulin resistance in mice that lack adipose tissue was reversed by a combination of leptin and adiponectin, but only partially by either protein alone (Nat Med 2001; 7: 941–46). In a separate study, Philipp Scherer (Albert Einstein College of Medicine, Bronx, NY, USA) and co-
A
late that low serum adiponectin levels before TZDs administration may serve as a sensitive marker to predict responsiveness to TZDs”, says Kadowaki. Evan Rosen (Dana-Farber Cancer Institute, Boston, MA, USA) notes that although there are likely to be several links between obesity and diabetes, decreased adiponectin secretion by fat cells in obesity looks as good as any other proposition to date. “The data appear convincing that it can reduce bodyweight, glucose, and insulin levels in obese diabetic mice”, he says. Although adiponectin is a protein, which makes it a less attractive candidate for use in human beings than other oral drugs in development, he stresses that a previous study (Proc Natl Acad Sci 2001; 98: 2005–10) has shown adiponectin to have one very special advantage over other potential drugs. “It causes weight loss. Almost all other antidiabetic drugs, including insulin, cause incidental weight gain, making them problematic for people who are overweight to begin with”, he says.
workers revealed that a single injection of adiponectin triggers a transient decrease in basal glucose concentrations in normal mice, and transiently abolishes hyperglycaemia in ob/ob and non-obese diabetic mice. This effect is not associated with an increase in insulin concentrations, and the researchers conclude that adiponectin reduces insulin resistance (Nat Med 2001; 7: 947–52). Both groups are now focusing on identification of the adiponectin receptor. Further studies in Scherer’s laboratory include generation of mouse models with genetically altered concentrations of adiponectin. “Since this is a protein with therapeutic, potential, future challenges will also include the production and delivery of sufficient amounts into the bloodstream”, he says. Kadowaki’s group is also interested in the adiponectin pathway as a therapeutic target. “Thiazolidinedione derivatives (TZDs) such as rosiglitazone and pioglitazone are potent adiponectin secretagogues and this may account for their actions as insulin-sensitiser and antidiabetic drugs. We also specu-
Kathryn Senior
Psychiatric disorders still evident in Bosnian refugees early half of former Bosnian refugees who remained living in the conflict region still show symptoms of psychiatric disorders and disability 3 years after initial assessment, report US researchers this week. “These findings reveal the serious chronic mental health impact of mass violence. In particular, depression was unremitting, disabling, and potentially associated with premature death in the elderly”, says Richard Mollica, one of the investigators. Mollica (Harvard Program in Refugee Trauma, MA, USA) and colleagues have followed the mental health impact of the recent war in Bosnia on a camp of Bosnian refugees (534 adults) who had initially found asylum in Croatia in 1996 and who are now returning home or are being resettled elsewhere in Europe and the USA. In their initial study, they reported a high rate of disability associated with depression and post-traumatic stress disorder (PTSD) among the refugees (JAMA 1999; 282: 433–39). Mollica and colleagues assessed whether these relations have continued over time and are associated
390
with mortality and further emigration. They report that at follow-up, 376 (70·4%) refugees remained living in the Balkans, 39 (7·3%) had died, 114 (21·3%) had emigrated, and 5 (1%) were lost to follow-up.
Rights were not granted to include this image in electronic media. Please refer to the printed journal. AP
N
Depression persists in Bosnian refugees
The investigators reinterviewed the refugees who had remained in the Balkans or the families of those who had died. 45% of the original respondents still had their psychiatric disorders. But only 16% of those who did not have symptoms of psychiatric disorder in 1996 had symptoms at follow-up. Refugees with depression had three times the risk of dying than those who were not depressed, but this relation was not significant after
adjustment for age, sex, and other factors. “The long-term impact of depression and PTSD on the development of cardiovascular disease and the potential for premature death in the elderly is a serious public health concern”, says Mollica. Refugees who emigrated were more traumatised, better educated, and had fewer health and mental-health problems than the majority who remained in the region (JAMA 2001; 286: 546–54). “These study results suggest the importance of early intervention in identifying and treating refugees with psychiatric disorders, especially depression”, says Mollica. Nathan Ford (Médecins Sans Frontières) agrees: “Mental health programmes should be seen as a core part of the emergency response to conflict, set up as early as possible during the emergency phase, because time is required to find and train local staff and understand the local context. It is vital to realise that an end to war does not mean an immediate return to normal life.” Minal Chande
THE LANCET • Vol 358 • August 4, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.