Association of oxygen consumption with insulin resistance among impaired glucose regulation and type 2 diabetes subjects
	
Background
Oxygen consumption is a measure of physical fitness which, in turn, is known to be an independent determinant of insulin sensitivity. So far the association of oxygen consumption with insulin resistance has not yet been adequately explored.

Aim
To get better insight on the issue we have investigated the association of oxygen consumption with insulin secretory capacity and insulin sensitivity among Impaired Glucose Tolerance (IGT), Impaired Glucose Regulation (ie. IGT, IFG-IGT), and Type 2 Diabetes Mellitus (T2DM) subjects with particular focus on the causal relationship of the two parameters.

Method
It was an observational analytical study with group comparison design involving Nondiabetic (ND) [ n=34, age (years) 39±9, BMI (kg/m2) 26±4, M±SD)], IGT [n=92, age (years) 41±9, BMI (kg/m2) 25±4, M±SD)]; IFG-IGT [(n= 27, age (years) 35±3, BMI (kg/m2) 26±4, M±SD)]; and T2DM [(n= 35, age (years) 43±9, BMI (kg/m2) 25±4, M±SD)] subjects. IGT, IFG-IGT and T2DM status were categorized as per WHO Study Group Criteria with 2-sample OGTT. Serum insulin was measured by chemiluminiscent ELISA technique. Insulin secretory capacity (HOMA% B) and insulin sensitivity (HOMA% S) were calculated from fasting glucose and fasting insulin values by homeostasis model assessment (HOMA) using HOMA-CIGMA software. Oxygen consumption was estimated by standard formula using a treadmill. Statistical comparisons between the groups were made by using ANOVA and Mann-Whitney U test. Pearson’s correlation was performed to explore the association of oxygen consumption with insulin sensitivity (HOMA% S) and insulin secretory capacity (HOMA% B) in the various study groups.

Results
Serum insulin levels [median (range)] in the various groups were as follows: ND 53.7 (15.3-156.3), IGT 55.1(13.9-223.6), IGR (IFG-IGT) 69.3 (15.3-313.2) and T2DM 67.1(13.9-266). The values did not differ between any two of the four groups. Insulin secretory capacity (HOMA% B) [median (range)] was 101(29-288) in IGT, 77 (25-221) in IFG-IGT, and 77 (27-161) in T2DM groups. HOMA% B in T2DM subjects were significantly lower (p=0.025) compared to the ND subjects [112 (34-247)]. T2DM and IFG-IGT also had significantly lower (p=0.030 and p=0.015 respectively) HOMA% B compared to the IGT subjects. On the other hand, only T2DM group had significantly lower (p=0.030) HOMA% S [median (range), 100 (16-306)] as compared to the ND group [median (range), 122 (48-308)]. Oxygen consumption [Median (range) (ml/kg/min)] was 17.8 (8.8-33.5) in ND, 16.2(8.2-33.5) in IGT, 16.2(8.2-33.5) in IFG-IGT and 13.8(8.8-18.8) in the T2DM groups. Oxygen consumption was significantly lower (p=0.003) in the T2DM as compared to the ND group. It was also lower in IGT and IFG-IGT as compared to the T2DM group (p=0.010 and p=0.030 respectively). A significant positive correlation was found between insulin sensitivity and oxygen consumption among the IFG-IGT (r=0.270, p=0.02) and T2DM subjects (r=0.460, p=0.001).

Discussion
DM subjects had significantly lower HOMA% S than the ND group. This seems to highlight of insulin resistance in the development of disturbed glucose homeostasis in DM subjects. So, DM and IFG-IGT subjects seem to have beta cell failure and relatively lower beta cell failure in IGT subjects. Insulin resistance may have in DM subjects evident by compromised HOMA % B and HOMA % S. In turn with this, physical fitness which is measured by oxygen consumption is a strong determinant of insulin sensitivity.  Oxygen consumption is lowered in both prediabetic and diabetic states and it seems to be a consequence of insulin resistance in these conditions.

Conflict of Interest
I have no potential conflict of interest to disclose