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Use of Dietary Sugars or Glucose Tablets in Correcting Hypoglycemia

Proponents may suggest an advantage of one over the other, but the data is not so clear.

With tighter control of blood glucose and lower recommended blood levels, the risk of development of hypoglycemia in the face of diabetes is on the rise, necessitating the use of self-administered treatments by diabetes patients who are experiencing mild to moderate symptomatic hypoglycemia.  To date, in the conscious hypoglycemic patient, the accepted method of correction has been administration of oral glucose, either in the form of commercially available tablets or dietary sugars. Until recently, the comparative benefits between these two treatment options has not been clearly determined, giving rise to the question, is there a clear advantage of one over the other?

To date, most studies investigating this issue have been quite small, and of questionable design. In a recent issue of the British publication Emergency Medicine Journal, investigators conducted a systematic review of the literature and identified 1,774 unique papers focused on effects of the treatment options on relief of symptomatic hypoglycemia, time to resolution, blood glucose levels, development of complications, and hospital lengths of stay (if admission were required as a result of the hypoglycemic episode).  Following a defined screening process, four total articles were selected for data pooling and meta-analysis. Three of the articles were randomized controlled trials, with the fourth being an observational study.  Statistical analyses were performed using the Mantel-Haenszel random-effects model to calculate heterogeneity (I2), pooled plots and treatment effect using risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes with 95% CIs.

The pooling of outcomes data was performed for the three RCTs involving 113 child and adult subjects having a total of 578 hypoglycemic events, with the primary outcome being resolution of hypoglycemia by 15 minutes following intervention. Comparator treatments were glucose tablets (15-20 gm) and dietary sugar sources including sucrose, fructose, orange juice, various candies (e.g. jelly beans, Skittles), and milk.  Statistical analysis favored glucose tablets over dietary sources in resolution of symptoms (RR 0.89, 95% CI 0.83 to 0.96).  The observational study included 13 adult subjects experiencing 22 events, and analysis also favored glucose tablets over dietary sugars (RR 0.3, 95% CI 0.68 to 0.86).  Subset analyses of the RCTs also compared glucose tablets against the specific dietary sugar types, showing no difference between glucose tablets and sucrose in the form of either Skittles or sugar lumps in resolution of symptoms (RR 0.99, 95% CI 0.91 to 1.07).  In the Slama study, the mean change in blood glucose was examined in 12 patients (6 in each arm) receiving either glucose tablets or sucrose dissolved in water, favoring glucose tablets (MD -0.90, 95% -1.78 to -0.02), while finding no difference between glucose tablets and chewed sucrose in the form of sugar lumps (MD 0.30, 95% CI -0.81 to 1.41). The other subset that favored glucose tablets was a comparison to fructose (Fruit To GoR) (RR 0.77, 95% CI -0.81 to 1.41).

Other sub-analyses that showed no difference in effect between glucose tablets and dietary sugar sources included comparisons to orange juice, jelly beans, Mentos, milk, and corn hydrolysate. Not surprisingly, a comparison of glucose tablets to glucose gel also showed no difference in correction of hypoglycemia.  Secondary outcomes including complications of hypoglycemia or effects on hospital lengths of stay were not reported in the four studies. Additionally, blood glucose levels and time to resolution were not reported in a manner sufficient enough to be included in the comparisons.

The authors concluded that diabetes patients displaying symptomatic hypoglycemia will display greater benefit from administration of commercially available oral glucose tablets over the grouped dietary sugar sources, and that use of tablets should be preferential.  They did correctly point out the limitations in the study, primarily the inclusion of only four studies with a very small population pool, underpowering the findings of the meta-analysis.  Additionally, the lack of standardization of sugar content in the examined dietary sources confounds the findings, adding a source of bias toward favoring glucose tablets.  In the end, the decisive conclusion favored glucose tablets as the clear choice.

This study has been presented on more than one occasion in favor of glucose tablets, yet is fraught with design issues already mentioned above.  Other problems included lack of children in the observational study (Brodows) and non-inclusion of type 2 diabetes patients in any study.  Until a large multi-center randomized trial can be performed, the conclusion that glucose tablets are clearly favorable over dietary sugars for treatment of hypoglycemia should be considered with caution.

Practice Pearls:

  • With tighter control of blood glucose, and decreasing target blood levels, hypoglycemia has become increasingly problematic.
  • Several forms of orally available glucose are at our disposal for treatment, but standardization of “glucose dosing” remains elusive.
  • Statistics may favor use of glucose tablets, but there is no clear advantage of tablets over dietary sources.

References:

Carlson JN, Schunder-Tatzber S, Neilson CJ, Hood N. Dietary sugars versus glucose tablets for first-aid treatment of symptomatic hypoglycemia in awake patients with diabetes: a systematic review and meta-analysis. Emerg Med J. 2017;34(2):100-106.

Husband AC, Crawford S, McCoy LA, Pacaud D. The effectiveness of glucose, sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes. Pediatr Diabetes. 2010;11(3):154-158.

McTavish L, Wiltshire E. Effective treatment of hypoglycemia in children with type 1 diabetes: a randomized controlled clinical trial. Pediatr Diabetes. 2011;12(4 Pt 2):381-387.

Slama G, Traynard PY, Desplanque N, et al. The search for an optimized treatment of hypoglycemia. Carbohydrates in tablets, solution, or gel for the correction of insulin reactions. Arch Intern Med. 1990;150(3):589-593.

Brodows RG, Williams C, Amatruda JM. Treatment of insulin reactions in diabetics. JAMA. 1984;252(24):3378-3381.
Mark T. Lawrence, RPh, PharmD Candidate, University of Colorado-Denver, School of Pharmacy NTPD