Brief report

Post-absorptive glucose lowering in normalhealthy individuals: An epidemiologicalobservation

Senthil K. Vasan a,b, Parthasarathy Ramachandran c,Mary Mathew c, Natraj C.V. c, Belavendra Antonisamy d, Nihal Thomas b,*aRolf Luft Centre for Diabetes, Department of Molecular Medicine & Surgery, Karolinska Institutet, Stockholm, SwedenbDepartment of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, Indiac Indian Institute of Science, Bangalore, IndiadDepartment of Biostatistics, Christian Medical College, Vellore, India

d i a b e t e s r e s e a r c h a n d c l i n i c a l p r a c t i c e 1 0 4 ( 2 0 1 4 ) e 5 – e 7

a r t i c l e i n f o

Article history:

Received 16 September 2013

Received in revised form

17 January 2014

Accepted 18 January 2014

Available online 4 February 2014

Keywords:

Hypoglycemia

Post-prandial

Insulin

Glucose

a b s t r a c t

Post-absorptive glucose lowering (PALG) is observed in individuals with glucose intolerance

and in healthy individuals. We report a prevalence of about 23% among healthy Asian

Indians. Individuals with PALG are characterized by leaner phenotype, low body fat per-

centage, increased insulin sensitivity and higher fasting glucose levels.

# 2014 Elsevier Ireland Ltd. All rights reserved.

Contents available at ScienceDirect

Diabetes Researchand Clinical Practice

journal homepage: www.elsevier.com/locate/diabres

Postprandial/post-absorptive plasma glucose levels are regu-

lated by insulin secretion and are usually maintained within a

range of 70–140 mg/dl (3.9–7.8 mmol/l), with postprandial

levels generally higher than fasting glucose in normal healthy

individuals. Asymptomatic lowering of postprandial blood

glucose is usually observed among individuals with abnormal

glucose tolerance and in patients on anti-diabetic medica-

tions, and less commonly (10–30%) in normal healthy

population [1–5]. In apparently healthy individuals, the

postprandial lowering is usually asymptomatic and symptoms

* Corresponding author at: Department of Endocrinology, Diabetes anTel.: +46 2282818.

E-mail address: nihal_thomas@yahoo.com (N. Thomas).

0168-8227/$ – see front matter # 2014 Elsevier Ireland Ltd. All rights

http://dx.doi.org/10.1016/j.diabres.2014.01.023

appear only when counter regulatory mechanisms are

unable to balance glucose disposal. The exact underlying

mechanism that leads to postprandial or post-absorptive

lowering of glucose (PALG) among healthy individuals

remains unknown. Early investigators have concluded it to

be an event of ‘‘no clinical significance, but a state of

transient biochemical abnormality’’ [6], while some argue it

is a state of impending diabetes [7]. The aim of the current

study was to estimate the prevalence of PALG in healthy

individuals and also investigate the difference in relationship

d Metabolism, Christian Medical College, Vellore 632004, India.

reserved.

Fig. 1 – Insulin and glucose response following OGTT in

PALG and normal individuals.

d i a b e t e s r e s e a r c h a n d c l i n i c a l p r a c t i c e 1 0 4 ( 2 0 1 4 ) e 5 – e 7e6

between body composition and insulin secretion pattern in

PALG and non-PALG group.

1. Research design/methods

The study included two independent cohorts from South

India, the Vellore Birth cohort (VBC; n = 2218, Age 26–32 years)

[8] and Office cohort (OC; n = 117, Age 18–22 years) [9]. Subjects

diagnosed with diabetes, IGT/impaired fasting glucose as

defined by WHO criteria or other related disorders/anti-

diabetic medication were excluded from the study. Data

relating to anthropometry and biochemical investigations

(glucose and insulin) were obtained. Glucose and insulin were

measured following a 75 g oral glucose tolerance test (OGTT)

using commercial enzymatic kits (Roche Diagnostics, Ger-

many) on a Hitachi 911 autoanalyser (USA) and immunor-

adiometric assay using Coat-a-Count kits (Diagnostic Products

Corporation, USA), respectively. The OC participants addi-

tionally had body fat percentage assessed using dual energy X-

ray absorptiometry (DXA). All participants signed the

informed consent and the institutional ethics committee

approved the study.

In the current study, biochemical PALG was defined when

120 min glucose was less than fasting glucose by 10 mg/dl

(0.6 mmol/l) and non-PALG when the 120 min glucose was

higher than fasting glucose by 10 mg/dl (0.6 mmol/l), similar to

previous criteria used by Cryer et al. [10].

2. Results

The overall prevalence of PALG was 22.8% of the total

population studied (22% and 24% in VBC and OC, respectively).

Clinical characteristics of the study population are summar-

ized in Supplement Table 1. Individuals with PALG had lower

BMI, lower waist circumference (WC) measurement and low

waist-hip ratio when compared to the non-PALG group

although statistically significance was observed only in the

VBC cohort for central adiposity measurement (WC) and BMI.

Body fat percentage measured using DXA in the OC partici-

pants further confirmed that the PALG group had lower total

body fat percentage compared to their non-PALG counterparts

(12.2% vs. 14.5%, p = 0.028). The OGTT demonstrated a steady

and sustained insulin secretion pattern at all-time points (30–

120 min) in non-PALG group, while a significant decline in the

insulin secretion from 30 min was observed in the PALG group

which corresponded to lower 120 min glucose levels (Fig. 1). No

difference in HOMA-IR was observed between the two groups

where as the Stumvoll Insulin Sensitivity Index was found to

be significantly higher for the PALG group ( p < 0.001).

3. Discussion

The study has two important observations (i) PALG is observed

in normal healthy individuals who have a leaner phenotype (ii)

these individuals with lower adiposity required relatively

lesser insulin to dispose an oral load of 75 g of glucose over 2 h

compared to normal individuals.

Saha et al. previously showed biochemical evidence of

lower blood glucose in the post absorptive state in apparently

healthy individuals from India [11]. We report a prevalence of

about 23% in healthy Indians, which is comparable to the

22.4% reported in healthy Japanese volunteers with lower BMI

[12] and greater than 12.4% reported in Caucasians [13]. Our

conclusions are based on a arbitrary cut-off for asymptomatic

hypoglycemia and differs from earlier reports where sympto-

matic hypoglycemia was reported by Fariss in 7.4% of healthy

individuals at a plasma glucose concentration below 49 mg/dl

(2.7 mmol/l) [3] and Hofeldt who noted 48% of normal subjects

with hypoglycemia symptoms had nadirs below 50 mg/dl

(2.8 mmol/l) [4,14]. Nevertheless, a consistent finding is that

PALG is a recognized phenomenon even among healthy

individuals and is associated with a thin-phenotype and

lower body fat percentage.

We additionally observed that despite similar fasting

insulin levels in both the groups, the area under the curve

(AUC)-insulin was lower and insulin sensitivity was higher in

PALG individuals compared to the non-PALG group which

points towards efficient glucose disposal among these

individuals who have a lower BMI. Increased insulin

sensitivity was also demonstrated using hyperinsulinemic-

euglycemic clamp in individuals with idiopathic reactive

hypoglycemia [15]. It should also be noted that insulin levels

mirror glucose levels and that difference in glucose absorp-

tion and consequently blood glucose levels may result in less

insulin secretion in the PALG group. Higher fasting glucose

levels could be due to enhanced counter-regulation through

the glucagon stimulation by gastro-intestinal peptide (GIP).

We acknowledge some limitations in our observations.

The diagnosis of PALG was based on a blood glucose

measurement at a single cross-sectional time point and

should be viewed with caution since marked variances in

glucose response on serial testing is common. This raises an

important question as to whether PALG is a transient

phenomenon or persistent over time in some individuals

d i a b e t e s r e s e a r c h a n d c l i n i c a l p r a c t i c e 1 0 4 ( 2 0 1 4 ) e 5 – e 7 e7

and whether this warrants a longitudinal follow-up. It could

be speculated that among individuals with persistent PALG, a

phenomenon such as ‘‘burnout’’ may co-exist in which an

over working glucose clearance system in lean individuals

may point to impending diabetes. It is also uncertain if this

response would be similar when tested using a mixed meal

tolerance test.

In conclusion, PALG is not an uncommon phenomenon

among normal individuals and is probably related to increase

insulin sensitivity in individuals with lower adiposity.

Conflict of interest

The authors declare that they have no conflict of interest.

Authors contribution

SKV, PR, MM, CVN, NT designed the study. PR analyzed the

data, SKV wrote the manuscript. All authors contributed to

further editing the paper and all authors reviewed the final

version of the manuscript and approved it. The study was

funded by the British Heart Foundation and Endocrinology-

Research grants from Christian Medical College, Vellore.

Appendix A. Supplementary data

Supplementary data associated with this article can be

found, in the online version, at http://dx.doi.org/10.1016/

j.diabres.2014.01.023.

r e f e r e n c e s

[1] Burns TW, Bregant R, Vanpeenan HJ, Hood TE. Observationson blood glucose concentration of human subjects duringcontinuous sampling. Diabetes 1965;14:186–93.

[2] Cahill Jr GF, Soeldner JS. A non-editorial on non-hypoglycemia. The New England Journal of Medicine1974;291(17):905–6.

[3] Fariss BL. Prevalence of post-glucose-load glycosuria andhypoglycemia in a group of healthy young men. Diabetes1974;23(3):189–91.

[4] Hofeldt FD. Transitional low blood glucose states. RockyMountain Medical Journal 1979;76(1):30–4.

[5] Hofeldt FD, Adler RA, Herman RH. Postprandialhypoglycemia. Fact or fiction? JAMA: The Journal of theAmerican Medical Association 1975;233(12):1309.

[6] Hofeldt FD. Reactive hypoglycemia. Endocrinology andMetabolism Clinics of North America 1989;18(1):185–201.

[7] Conn JW, Fajans SS, Seltzer HS. Spontaneous hypoglycemiaas an early manifestation of diabetes mellitus. Diabetes1956;5(6):437–42.

[8] Antonisamy B, Raghupathy P, Christopher S, Richard J,Rao PS, Barker DJ, et al. Cohort profile: the 1969–73 Vellorebirth cohort study in South India. International Journal ofEpidemiology 2009;38(3):663–9.

[9] Thomas N, Grunnet LG, Poulsen P, Christopher S, SpurgeonR, Inbakumari M, et al. Born with low birth weight in ruralSouthern India: what are the metabolic consequences 20years later? European Journal of Endocrinology/EuropeanFederation of Endocrine Societies 2012;166(4):647–55.

[10] Cryer PE, Santiago JV, Shah S. Measurement ofnorepinephrine and epinephrine in small volumes ofhuman plasma by a single isotope derivative method:response to the upright posture. The Journal of ClinicalEndocrinology and Metabolism 1974;39(6):1025–9.

[11] Saha B. Post prandial plasma glucose level less than thefasting level in otherwise healthy individuals duringroutine screening. Indian Journal of Clinical Biochemistry:IJCB 2006;21(2):67–71.

[12] Sasaki M, Mogi T, Wada Y, Hirosawa I, Koizumi A. Anendemic condition of biochemical hypoglycemia amongmale volunteers. Industrial Health 1996;34(4):323–33.

[13] Sorensen M, Johansen OE. Idiopathic reactivehypoglycaemia – prevalence and effect of fibre on glucoseexcursions. Scandinavian Journal of Clinical andLaboratory Investigation 2010;70(6):385–91.

[14] Hofeldt FD. Reactive hypoglycemia. Metabolism: Clinicaland Experimental 1975;24(10):1193–208.

[15] Tamburrano G, Leonetti F, Sbraccia P, Giaccari A,Locuratolo N, Lala A. Increased insulin sensitivity inpatients with idiopathic reactive hypoglycemia. TheJournal of Clinical Endocrinology and Metabolism1989;69(4):885–90.