Glucose not responsible for inflammation in type 2 diabetes
To date, the underlying causes of inflammation in obesity and type 2 diabetes mellitus (T2DM) have been poorly understood, but a new research seems to have made a breakthrough by finding that that changes to mitochondria--the powerhouse of cells--drive chronic inflammation from cells exposed to certain types of fats, shattering the prevailing assumption that glucose was the culprit.
According to the study, chronic inflammation fuels many of the devastating complications of type 2 diabetes, including cardiovascular, kidney, periodontal diseases, and is thus one of the key targets for therapy development.
This new data may enlighten the conversation about tight glycemic control as the dominant treatment goal for people with diabetes.
Research didn't set out to disprove the glucose-inflammation causation theory.
Based on the importance of glycolysis--a 10-reaction sequence that produces energy--in other types of inflammation, the team hypothesised those immune cells from patients with type 2 diabetes would produce energy by burning glucose. "We were wrong," he said.
"We exclusively used immune cells from human subjects for all of the work," he explained, noting that humans, but not animal models of type 2 diabetes, have the specific pro-inflammatory T cell profile her team had identified in earlier research.
The team was surprised to find that glycolysis wasn't driving chronic inflammation. Instead, a combination of defects in mitochondria and elevated fat derivatives were responsible.
Nikolajczyk said she sees applications for this research in both basic and clinical sciences. She hopes to precisely define pro-inflammatory lipid types and explore associations between circulating and/or tissue-associated lipids and insulin resistance, one key feature of Type 2 diabetes.
She is also interested in contributing to the development of new analytical approaches, spearheaded by Dr. Lauffenburger's team, that leverage ongoing lipid-related findings into a new understanding of pathology in type 2 diabetes.
"Aggressive blood glucose control to lower the risk of diabetic complications has been the goal for most people with Type 2 Diabetes for decades. Our data provide an explanation for why people with tight glucose control can nonetheless have disease progression," Nikolajczyk said.
Family history of diabetes associated with increased bone mineral density
The association between type 2 diabetes and increased fracture risk is well documented. However, little was known about the possible effect of family history of diabetes on bone mineral density (BMD). A study from China now confirms that a history of first-degree family members with diabetes is linked to increased BMD as well as to insulin resistance. Results are published online in Menopause, the journal of The North American Menopause Society (NAMS).
Because patients with type 2 diabetes are at an increased risk of fracture, understanding the early pathophysiology of altered BMD could be critical in the development of preventive strategies for diabetic osteoporosis. Although strong evidence has revealed normal to high BMD in most patients with type 2 diabetes, no data have been published, to date, that demonstrate whether BMD is altered in persons with a first-degree family history of diabetes.
In this new study involving nearly 900 normoglycemic postmenopausal women, it was found that the BMD of the lumbar spine and femoral neck was significantly higher in participants with a first-degree family history of diabetes than in those without such history, even in women with normal blood glucose levels. These same participants additionally showed increased insulin resistance and hyperinsulinemia.
"This study shows an association between a family history of diabetes and increased bone density in postmenopausal women. This finding may be related to higher insulin levels in these women with a hereditary predisposition to diabetes, because insulin has a bone-building effect. Although this sounds like good news, these women are at increased risk for developing diabetes, which is associated with skeletal fragility and increased fracture risk," says Dr. Stephanie Faubion, NAMS medical director.
According to the study, chronic inflammation fuels many of the devastating complications of type 2 diabetes, including cardiovascular, kidney, periodontal diseases, and is thus one of the key targets for therapy development.
This new data may enlighten the conversation about tight glycemic control as the dominant treatment goal for people with diabetes.
Research didn't set out to disprove the glucose-inflammation causation theory.
Based on the importance of glycolysis--a 10-reaction sequence that produces energy--in other types of inflammation, the team hypothesised those immune cells from patients with type 2 diabetes would produce energy by burning glucose. "We were wrong," he said.
"We exclusively used immune cells from human subjects for all of the work," he explained, noting that humans, but not animal models of type 2 diabetes, have the specific pro-inflammatory T cell profile her team had identified in earlier research.
The team was surprised to find that glycolysis wasn't driving chronic inflammation. Instead, a combination of defects in mitochondria and elevated fat derivatives were responsible.
Nikolajczyk said she sees applications for this research in both basic and clinical sciences. She hopes to precisely define pro-inflammatory lipid types and explore associations between circulating and/or tissue-associated lipids and insulin resistance, one key feature of Type 2 diabetes.
She is also interested in contributing to the development of new analytical approaches, spearheaded by Dr. Lauffenburger's team, that leverage ongoing lipid-related findings into a new understanding of pathology in type 2 diabetes.
"Aggressive blood glucose control to lower the risk of diabetic complications has been the goal for most people with Type 2 Diabetes for decades. Our data provide an explanation for why people with tight glucose control can nonetheless have disease progression," Nikolajczyk said.
Family history of diabetes associated with increased bone mineral density
The association between type 2 diabetes and increased fracture risk is well documented. However, little was known about the possible effect of family history of diabetes on bone mineral density (BMD). A study from China now confirms that a history of first-degree family members with diabetes is linked to increased BMD as well as to insulin resistance. Results are published online in Menopause, the journal of The North American Menopause Society (NAMS).
Because patients with type 2 diabetes are at an increased risk of fracture, understanding the early pathophysiology of altered BMD could be critical in the development of preventive strategies for diabetic osteoporosis. Although strong evidence has revealed normal to high BMD in most patients with type 2 diabetes, no data have been published, to date, that demonstrate whether BMD is altered in persons with a first-degree family history of diabetes.
In this new study involving nearly 900 normoglycemic postmenopausal women, it was found that the BMD of the lumbar spine and femoral neck was significantly higher in participants with a first-degree family history of diabetes than in those without such history, even in women with normal blood glucose levels. These same participants additionally showed increased insulin resistance and hyperinsulinemia.
"This study shows an association between a family history of diabetes and increased bone density in postmenopausal women. This finding may be related to higher insulin levels in these women with a hereditary predisposition to diabetes, because insulin has a bone-building effect. Although this sounds like good news, these women are at increased risk for developing diabetes, which is associated with skeletal fragility and increased fracture risk," says Dr. Stephanie Faubion, NAMS medical director.