The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 3 796-800
Copyright © 1998 by The Endocrine Society
Gin and Tonic and Reactive Hypoglycemia: What Is Important–the Gin, the Tonic, or Both?1
Daniel Flanagan,
Peter Wood,
Robert Sherwin,
Kwasi Debrah and
David Kerr
Metabolism Unit, Royal Bournemouth Hospital, Bournemouth, England;
Endocrinology Laboratory, Southampton General Hospital (P.W.), and the
Division of Endocrinology, Yale University School of Medicine (R.S.),
New Haven, Connecticut 06520
Address all correspondence and requests for reprints to: Dr. David Kerr, Metabolism Unit, Royal Bournemouth Hospital, Castle Lane East, Bournemouth, Dorset, England BH7 7DW. E-mail:
diabet{at}rbch-tr.swest.nhs.uk
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Abstract
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The objectives of this study were to test the hypothesis that alcohol
can cause reactive hypoglycemia by attenuating the release of
counterregulatory hormones. The subjects were eight healthy volunteers
(five men and three women, aged 20–40 yr). Each subject drank, using a
randomized, double blind design 1) three large gin with regular tonics
(0.5 g/kg alcohol and 60 g carbohydrate, mainly sucrose (G+T); 2)
the same amount of alcohol with Slim-line tonic (0.5 g carbohydrate; G
alone); and 3) regular tonic without alcohol (T alone). Glucose,
insulin, and counterregulatory hormone levels and middle cerebral
artery velocity (MCAV), an index of cerebral blood flow, were
measured.
Alcohol levels averaged 60–70 mg/dL. Peak insulin levels were similar
in both studies in which regular tonic was consumed (95% confidence
interval for difference, -6 to 22 µU/mL). After the ingestion of
G+T, the blood glucose nadir was lower compared to that with T alone
(3.35 vs. 3.87 mmol/L; P < 0.02) or
G alone (3.35 vs. 3.95 mmol/L; P <
0.01). After drinking gin, subjects reported typical hypoglycemic
warning symptoms unrelated to the prevailing glucose level. In both
alcohol studies, there was marked blunting of GH release
(P < 0.01). Despite a blood glucose nadir of 3.35
mmol/L, plasma epinephrine levels rose only slightly from 267 to 455
pmol/L (P = NS) after G+T. Ingestion of alcohol
also caused a transient rise in right MCAV (P <
0.05) followed by a late drop in velocity in both cerebral hemispheres
in the G+T study (P < 0.05).
In otherwise healthy individuals a combination of gin and regular tonic
can induce reactive hypoglycemia. Acute ingestion of alcohol impairs
the epinephrine response and markedly suppresses the release of GH in
response to a fall in blood glucose levels.
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Introduction
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TWENTY years ago, O’Keefe and Marks
examined the metabolic consequences of drinking two or three large gin
and tonics as a "liquid lunch." The combination of gin and a mixer
of regular tonic containing 60 g sucrose caused profound reactive
hypoglycemia (mean blood glucose nadir, 2.7 mmol/L) up to 3–4 h
afterward. Mixing alcohol with low calorie tonic or drinking regular
tonic on its own had much less of an effect on blood glucose levels
(1).
The aim of this study was to test the hypothesis that hypoglycemia
occurs not only as a result of hyperinsulinemia but also because of
blunting of normal counterregulatory hormone release.
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Methods
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Eight healthy volunteers (five men and three women, aged 20–40
yr), whose weekly alcohol consumption was less than 14 U, gave written
consent for the study, which was approved by the local hospital ethics
committee. After an overnight fast, 3 days of abstention from alcohol,
and resting semirecumbent for 30 min, a retrograde, venous catheter was
inserted into the dorsum of the nondominant hand with the hand placed
in a "hot box" at 60 C to arterialize venous blood. The cannula was
kept patent with a constant infusion of 0.9% saline. Using a
randomized, double blind design, each subject participated in three
studies separated by at least 2 weeks. They drank 1) 730 mL regular
Indian tonic water (Sainsbury, London, UK) containing 60 g
carbohydrate mainly as sucrose plus 0.5 g/kg ethanol as Beefeater Gin
equivalent to 97 mL for a 70-kg man (G+T), 2) 730 mL Slim-line tonic
(Sainsbury, London, UK) containing 0.5 g carbohydrate plus gin as
described above (G alone), and 3) 730 mL regular Indian tonic water
containing 60 g carbohydrate alone (T alone).
Over the next 300 min, the following measurements were made at 30- to
60-min intervals: 1) blood alcohol by gas liquid chromatography; 2)
right and left middle cerebral artery velocity, an index of cerebral
blood flow, using a trans-cranial Doppler technique (SciMed, Bristol,
UK) (2); 3) heart rate and blood pressure using an oscillometric
sphygmomanometer; and 4) levels of plasma insulin and the
counterregulatory hormones: catecholamines, GH, and cortisol. Plasma
insulin [intraassay coefficient of variation (CV), 7.2% at 14.2
µU/mL], cortisol (intraassay CV, 6.8 at 382 nmol/L), GH (intraassay
CV, 6.2% at 7.8 µU/L), and glucagon (intraassay CV, 10.9% at 40
ng/L) levels were measured by double antibody RIA. Catecholamines were
measured by a radioenzymatic technique (Amersham, Arlington Heights,
IL; epinephrine intraassay CV, 18% at 46 pg/mL; norepinephrine
intraassay CV, 10% at 210 pg/mL). Symptoms of hypoglycemia were also
determined. Subjects completed 100 mm visual analogue assessment of
symptoms characteristically associated with hypoglycemia (facial
flushing, palpitations, tingling, trembling, sweating, hunger,
lightheadedness, weakness, anxiety, difficulty concentrating, and
tiredness). Whole blood glucose was measured at 15-min intervals by a
glucose oxidase method (Yellow Springs Instrument Co., Yellow Springs,
OH; interassay CV, 4.0% at 4.2 mmol/L).
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Statistical analyses
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Overall differences between serial measurements were examined by
summary measures (3). Summary responses for each individual were
calculated as the area under the curve. Contrasts in group means were
compared by repeated measures ANOVA or, where appropriate, by paired
Student’s t tests. Where data were not normally
distributed, comparisons were made after logarithmic transformation or
Wilcoxon signed rank tests. Results are expressed as differences
between means and 95% confidence intervals (CI). Otherwise, data
are shown as the mean ± SE or median (interquartile
range).
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Results
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Blood glucose, plasma insulin, and levels of
counterregulatory hormone levels were similar at the start of each
study. After ingestion of gin, blood alcohol levels rose rapidly to
60 ± 5 and 66 ± 6 mg/dL in the G+T and G alone studies,
respectively. As expected, blood glucose and insulin excursions were
more substantial after drinking regular tonic (G+T and T alone studies;
Fig. 1
). However, nadir blood glucose
levels were lower after drinking G+T compared to either G alone (3.35
vs. 3.95 mmol/L; mean difference, 0.60; 95% CI, 0.41 to
0.79 mmol/L; P < 0.01) or T alone (3.35 vs.
3.87 mmol/L; mean difference, 0.52 mmol/L; 95% CI, 0.23–0.81;
P < 0.02; Table 1).
Insulin levels were markedly higher in both studies where regular tonic
was consumed [peak level after G+T, 51 vs. 17 µU/mL;
after G alone, 34 µU/mL (95% CI, 17–52; P < 0.02);
peak level after T alone, 43 vs. 17 µU/mL; 26 µU/mL
(95% CI, 11–41; P < 0.02)]. The rise in plasma
insulin levels was similar in the G+T and T alone studies (95% CI
for difference, -6 to 22 µU/mL; P = NS).
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Figure 1. Blood glucose (upper panel)
and plasma insulin levels at baseline and over the subsequent 300 min.
Results are shown as the mean ± SE.
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Overall epinephrine, norepinephrine, cortisol, and glucagon
responses were similar in each of the three studies, whereas plasma GH
levels were markedly suppressed by alcohol on both occasions (Table 2 and Fig. 2). Despite a blood glucose nadir of 3.35
mmol/L, plasma epinephrine levels only increased from 267 to 455 pmol/L
(+178 pmol/L; CI, -20 to 395; P = NS) and were
unchanged from baseline in the other two studies. Levels of other
counterregulatory hormones and norepinephrine were similar in all three
studies.
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Figure 2. Plasma GH levels at baseline and over the
subsequent 300 min. Results are shown as the mean ±
SE.
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In both alcohol studies, there was a transient rise in right
middle cerebral artery velocity followed by a late fall in velocity in
both hemispheres in the G+T study (Fig. 3). Drinking G+T was also associated with
a greater rise in heart rate [after G alone: 11.3 vs. 6.8;
4.5 beats/min (CI, 1.8–77.2); after T alone: 11.3
vs. 5.1; 6.2 beats/min; (CI, 1.2–11.2; both
P < 0.05)] and fall in mean arterial pressure [after
G alone: -10 vs. -6; -4 mm Hg; (CI, -2 to -7); after T
alone: -10 vs. -5; -5 mm Hg; (CI, -1 to -7; both
P < 0.05)]. After alcohol, the subjects reported an
increase in dizziness, tingling, difficulty thinking, and sweating
symptoms unrelated to the prevailing blood glucose level, with
cumulative symptom scores greater in both alcohol studies (533 and 511
vs. 283 in the Talone study; P < 0.01)
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Figure 3. Changes in right (upper
panel) and left middle cerebral artery velocity. Results are
expressed as the percent change ±SE from baseline for each
study. *, P < 0.05 for G+T and G alone studies
vs. T alone; #, P < 0.05 for G+T
vs. G alone and T alone.
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Discussion
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Almost 20 yr ago, O’Keefe and Marks reported that drinking a
combination of gin and regular tonic (equivalent to three double
measures) could cause reactive hypoglycemia many hours later, possibly
as a result of direct priming of pancreatic ß-cells by alcohol (1).
Here, we have confirmed their original observation that a combination
of alcohol and a mixer containing a large amount of carbohydrate is
more likely to cause reactive hypoglycemia than drinking either the gin
or the mixer on its own. This did not appear to be due to greater
hyperinsulinemia. In both alcohol studies, there was marked suppression
of plasma GH levels when blood glucose declined below baseline.
Drinking gin and regular tonic also caused an early transient rise in
heart rate and fall in blood pressure and a later reduction in arterial
velocity in both hemispheres.
Previous studies have reported that acute and sustained alcohol
use can suppress GH release in response to insulin-induced
hypoglycemia, arginine, and propranolol-glucagon (4, 5, 6). At night,
acute and chronic alcohol administration is associated with a 75%
reduction in the usual nighttime sleep-related release of GH (7). GH is
an insulin antagonist; suppression may therefore lead to increased
insulin sensitivity and a lower blood glucose level. Furthermore, after
gin and regular tonic, plasma epinephrine levels did not rise
significantly despite a blood glucose nadir below the blood glucose
threshold for release of epinephrine (8). In healthy volunteers, it
would be anticipated that there would be a 3- to 4-fold increase in
epinephrine levels associated with the degree of hypoglycemia achieved
here (9). However, we cannot entirely confirm the apparent lack of
response, as comparable hypoglycemia was not achieved in each
individual.
After acute ingestion of moderate amounts of alcohol, most studies have
shown an increase in heart rate, probably as a reflex response to
arteriolar or venous dilatation (10). As noted by others (11, 12),
acute ingestion of alcohol caused a transient rise in right middle
cerebral artery velocity, an index of cerebral blood flow. The
reduction in MCAV occurred around the same time as blood glucose levels
fell below baseline and thus could be considered maladaptive, as it
would be expected that cerebral blood flow would be maintained in the
face of systemic hypoglycemia to maintain substrate supply to the
brain. All three drinks contained quinine, which has been implicated in
causing hypoglycemia (13), but the dose was small (59 mg/drink) and
unlikely to be significant.
In conclusion, drinking a combination of gin and regular tonic can
cause a fall in blood glucose levels into the hypoglycemic range
associated with suppression of GH release. It is possible that the
involvement of alcohol in road traffic and other accidents may be a
consequence of neuroglycopenia as well as a result of the well
recognized direct effects of acute ingestion of alcohol on the
brain.
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Acknowledgments
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The authors thank Aida Grossman for help with measurement of
plasma catecholamine levels, and June Murphy for her assistance with
the smooth running of the studies.
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Footnotes
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1 This work was supported by grants from the Wessex Medical Trust and
the National Institutes of Health (DK-20495). 
Received September 4, 1997.
Revised November 13, 1997.
Accepted November 18, 1997.
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White NJ, Warrell DA, Chanthavanich P, et al. 1983 Severe hypoglycemia and hyperinsulinemia in falciparum malaria. N
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Abstract
Introduction
