Dose and time-response effect of photobiomodulation therapy on glycemic control in type 2 diabetic patients combined or not with hypoglycemic medicine: A randomized, crossover, double-blind, sham-controlled trial

Abstract

Photobiomodulation therapy (PBMt) combined or not with oral hypoglycemic medication has not been investigated in type 2 diabetes (T2DM) patients. All 10 T2DM patients were assessed randomly at 6 different occasions (3 with and 3 without regular oral hypoglycemic medication). Capillary glycemia was assessed after overnight fast (pre-prandial), 1 h postprandially (standardized meal, 338 kcal), and 30 min, 3 h, 6 h, 12 h post-PBMt (830 nm; 25 arrays of LEDs, 80 mW/array). Three doses (0 J-sham, 100 J, 240 J per site) were applied bilaterally on quadriceps femoris muscles, hamstrings, triceps surae, ventral upper arm and forearm; and randomly combined or not with oral hypoglicemic medication, totaling six different therapies applied for all 10 TDM2 patients (PBMt sham, PBMt 100 J, PBMt 240 J, PBMt sham + medication, PBMt 100 J + medication, PBMt 240 J + medication). Cardiac autonomic control was assessed by heart rate variability (HRV) indices. Without medication, there was reduction in glycemia after all PBMt doses, with 100 J as the best dose that persisted until 12 h and presented lower area under the curve (AUC). With medication, glycemia decreased similarly among doses. No differences between 100 J and sham + medication, but AUC was significantly lower after 100 J, suggesting better glycemic control. Low frequency component of HRV increased after sham + medication and 100 J, suggesting higher sympathetic activation. PBMt showed time- and dose-response effect to reduce glycemia in T2DM patients. Effects on HRV were consistent with glycemic control.

Keywords: dose-response; glycemic control; heart rate variability; hypoglycemic drugs; insulin resistance; photobiomodulation therapy.

Figure 1.

Study design. PBMt – photobiomodulation therapy; HRV – heart rate variability.

Figure 2.

Light-emitting device composed of 200 low-intensity LEDs (light-emitting diodes), containing 25 arrays of 4 LEDs in the red range and 25 arrays of 4 LEDs in the near-infrared range. Only near-infrared light was used in this study. Example of irradiation on the quadriceps femoris muscles.

Figure 3.

Capillary glycemia after an overnight fast (pre-prandial) and after a standardized meal (post-prandial), without oral hypoglycemic medication intake (no medication) or after oral hypoglycemic medication intake (medication) in type 2 diabetic patients (n=10). ****p<0.0001 vs pre-prandial. Values are average and standard error of the mean.

Figure 4A –

Change in glycemia response (delta) after the standardized meal (1 hour postprandial), and 30 min, 3, 6, and 12 hours after 0 J (sham), 100 J or 240 J of photobiomodulation therapy (PBMt), in type 2 diabetes patients without oral hypoglycemic medication (n=10). Values are average and standard error of the mean. 4B – Area under the curve (n=10). Values are arbitrary units. Within group comparison vs 1 hour postprandial: #p<0.05 for sham, *p<0.05 for 100 J, $ p<0.05 for 240 J. Between groups comparisons: ‡ p<0.05 vs sham, ∯ p<0.05 vs 240 J.

Figure 5A –

Delta glycemia response after a standardized meal (1 hour postprandial), and 30 min, 3, 6, and 12 hours after 0 J (sham), 100 J or 240 J of PBMt, in type 2 diabetes patients associated with oral hypoglycemic medication intake (n=10). Values are average and standard error of the mean. 5B – area under the curve (n=10). Values are arbitrary units. Between groups comparisons vs 1 hour postprandial: #p<0.05 for sham, *p<0.05 for 100 J, $ p<0.05 for 240 J.

Figure 6 –

Glycemia area under the curve without or with oral hypoglycemic medication intake combined with PBMt: sham (0 J) (6A); PBMt 100 J (6B); or PBMt 240 J (6C); (n=10). **p<0.01. Values are arbitrary units.

Figure 7 –

Delta glycemia response after a standard meal (1 hour postprandial), and 30 min, 3, 6, and 12 hours after PBMt sham (0 J) combined with oral hypoglycemic medication intake, and after PBMt 100 J without oral hypoglycemic medication intake in type 2 diabetes patients (n=10) (7A) - values are average and standard error of the mean. Area under the curve (7B) - values are arbitrary units. Rate of glucose decay (7C) - values are average and standard error of the mean. *p<0.05, **p<0.01.