Researchers have found molecular evidence1 to answer why some type 2 diabetics who appear lean are actually 'metabolically obese'.
Overweight and obesity are known to be important risk factors for diabetes and cardiovascular diseases. In Asia, obesity rates do not directly correspond with diabetes rates. India has a low prevalence of obesity but notably high rates of type 2 diabetes.
In Asian populations, a higher risk of diabetes starts at a lower body mass index than in Europeans. Thus, one of the factors that contributes to the diabetes epidemic in Asians is the 'normal-weight metabolically obese' phenotype. Till now, the biochemical or molecular basis for 'metabolic obesity' was poorly understood.
To probe this, the researchers measured the size of fat cells (adipocytes) from human visceral and subcutaneous fats and found that lean diabetics had higher adipocyte cell size (adipocyte hypertrophy) than control subjects. Also, adipose tissue from these lean diabetics showed faster aging (senescence) as evident from their shortened telomeres. They also had a secretory profile going by the low levels of adiponectin, the protein involved in regulating glucose levels as well as fatty acid breakdown.
"When such fat cells switch to a senescent and proinflammatory phenotype, they also change their job from 'fat storage' to 'fat spillage'. This fat accumulation complicates functioning of several other organs including the heart and triggers cardiovascular disease in diabetes patients" says lead researcher Muthuswamy Balasubramanyam. The study exposes adipocyte hypertrophy and senescence as targets for new drug discoveries, he adds.
The research urges timely prevention and management to reduce adverse outcomes in all patients with type 2 diabetes, particularly in metabolically obese normal-weight patients, who may have a false sense of protection because they are not overweight or obese.
The authors of this work are from: Madras Diabetes Research Foundation, Chennai, Dr. Mohan's Diabetes Specialities Centre, Chennai & LifeLine Multi-Speciality Hospitals, Chennai, India.
