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Diabetes & Obesity International Journal Research Article 3 min read

Non-Obese South Asians with Diabetes: A Pathophysiological Conundrum

Misra A* and Anoop S*
* Corresponding author
ISSN: 2574-7770  10.23880/doij-16000124  Received: August 26, 2016  Published: September 06, 2016
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Keywords
Pathophysiological Conundrum Diabetes T2DM
Abstract

Type 2 diabetes mellitus (T2DM) is one of the leading causes of mortality and mortality in developing countries. Globally, a rising trend in type 2 diabetes, usually related to obesity, is being witnessed in young adults, including South Asians.

Editorial

South Asians [1].In South East Asia, nearly 1.2 million
deaths were attributed to T2DM.The number of people

South Asians as compared to white Caucasians [9]. In an obese person with body composition as mentioned above, insulin resistance leads to dysmetabolic state, resulting in diabetes. In non-obese persons the pathophysiology for the development of diabetes is unclear. Interestingly, even ‘non-obese’ persons (BMI<25kg/m2) may have dysmetabolic state due to their body composition. Such person’s often termed as ‘metabolically obese normal weight’ (similar phenotype as of Asian Indians), actually have higher proportion of body fat, located primarily at truncal-abdominal depots (truncal subcutaneous, pericardiac and intra-abdominal depots and the liver). Our observations on young non-obese Asian Indians with type 2 diabetes shows increased total abdominal fat (19.4%), total intra-abdominal fat (49.7%), intra- peritoneal fat (47.7%) and retroperitoneal fat (70.7%) as compared to BMI matched non-diabetic controls [10]. In such ‘non obese’ persons, excess accumulation of hepatic fat assumes importance. A strong relationship exists between hepatic steatosis and insulin resistance [11]. We have previously shown that non-obese, non- diabetic Asian Indians with Non-Alcoholic fatty liver (NAFLD) have deranged gluconeogenesis, as investigated using proton magnetic resonance spectroscopy [12]. Remarkably, Asian Indians have more than two fold excess hepatic triglyceride content and lower insulin sensitivity as compared to Caucasian men [13]. Further, in a detailed MRI study, in non -obese Asian Indians with T2DM, we recently reported increased liver span (a surrogate marker of hepatic fat), correlated with increased intra-abdominal fat volume as compared to non- obese controls [10]. Overall, presence of NAFLD in a non-obese patient has important implications for development of type 2 diabetes. A less investigated area is ectopic fat deposition in the pancreas (‘fatty pancreas”) and its association with insulin resistance, insulin secretion and diabetes. Three out of five MRI-based studies on pancreas, including ours [10] have reported increased pancreatic volume in patients with type 2 diabetes as compared to controls [14, 15, 16]. Specifically, we reported 26% higher pancreatic volume (a surrogate marker of fat deposition in pancreas) in young, non-obese, Asian Indians with type 2 diabetes as compared to BMI-matched non-diabetic controls. Further, increased pancreatic volume correlated with intra- abdominal fat and liver span in these patients [10]. Increased abdominal adiposity and large adipocyte size [9] in Asian Indians lead to increased release of non- esterified free fatty acids (NEFAs) as compared to Whites [17]. Importantly, NEFAs overload in islet cells of the pancreas leads to impaired beta cell response to hyperglycemia. Prolonged hyperglycemia and lipotoxicity may result in fatty deposit, fibrosis, and deranged functions of pancreatic islet cells; effects similar to steato- necrosis in the liver. It is noteworthy that fat infiltration in the pancreas may impair beta cell response to hyperglycemia [18]. Notably, Asian Indians with impaired glucose tolerance may have declining beta cell function, irrespective of age, adiposity, insulin sensitivity, or family history of diabetes [19, 20], and infiltration of fatty tissue in pancreas could further may contribute to it, or worsen it. This phenomenon has important clinical implications especially in the clinical management of diabetes in non- obese Asian Indians where both insulin resistance and insulin secretory defect should be kept in relationship at "fatty pancreas" with diabetes consideration while formulating management strategy. No doubt there are other, most notably genetic factors, to consider. For instance, the association of the TCFL 2 variants has been implicated in WNT signaling, secretion and pancreatic development [21] and many other need further research and consideration in pathogenesis of diabetes in non-obese Asian Indians with diabetes.

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@article{misra2016,
  title   = {Non-Obese South Asians with Diabetes: A Pathophysiological Conundrum},
  author  = {Misra A* and Anoop S},
  journal = {Diabetes & Obesity International Journal},
  year    = {2016},
  volume  = {1},
  number  = {2},
  doi     = {10.23880/doij-16000124}
}
Misra A* and Anoop S (2016). Non-Obese South Asians with Diabetes: A Pathophysiological Conundrum. Diabetes & Obesity International Journal, 1(2). https://doi.org/10.23880/doij-16000124
TY  - JOUR
TI  - Non-Obese South Asians with Diabetes: A Pathophysiological Conundrum
AU  - Misra A* and Anoop S
JO  - Diabetes & Obesity International Journal
PY  - 2016
VL  - 1
IS  - 2
DO  - 10.23880/doij-16000124
ER  -