Hypoglycemia: Risk factors and Ramadan
medwireNews: Results presented during an EASD annual meeting session on hypoglycemia covered risk factors and consequences, and looked at the optimal insulin management approach for diabetes patients wishing to observe Ramadan.
Researcher Mohammed Hassanein (Dubai Health Authority, United Arab Emirates) said that more than 100 million diabetes patients are thought to observe Ramadan, with the length of the daily fast (during daylight hours) ranging from 12 to 20 hours depending on location.
His team’s randomized trial of 263 insulin-dependent patients with type 2 diabetes found that insulin degludec/insulin aspart was associated with a significant 62% reduced risk for severe or blood glucose-confirmed hypoglycemia, compared with biphasic insulin aspart, during the 4 weeks of Ramadan and a 74% reduced risk across the whole study period, which ran from 8–20 weeks before to 4 weeks after Ramadan. There was also an 83% reduced risk for nocturnal hypoglycemia.
Although blood glucose levels with both insulins were fairly similar across the day during Ramadan, levels in patients using biphasic insulin aspart dropped significantly lower than in those using insulin degludec/insulin aspart at a critical time of day: right at the end of the fasting period just before the evening meal, when blood glucose was at its lowest.
Glycated hemoglobin (HbA1c) levels fell by a similar amount (about 1.1%) with both insulins during the pre-Ramadan period and remained stable during Ramadan.
Two studies in this session looked at risk factors for hypoglycemia: weight gain and glycemic variability. In one, Anisoara Bumbu (Bichat Hospital, Paris, France) described research using data from the DCCT to explore the consequences of weight gain, which was associated with intensive glucose control in the trial.
The average weight gain among all 1441 patients over 6.5 years of follow-up was 1.2 kg/annum and 7.4 kg in total, and this significantly correlated with patients’ hypo-score, which was the number of hypoglycemic blood glucose measurements divided by the total number of measurements. The association persisted after accounting for variables including age, diabetes duration, and BMI at baseline, with patients in the top two tertiles of hypo-score significantly more likely to gain at least 1.8 kg/year than those in the bottom tertile. And it remained significant after further adjustment for change in HbA1c levels during the first year.
Bumbu said the mechanism underlying the association is not clear; delegates suggested possibilities including variation in insulin dose and patients snacking to recover from hypoglycemic episodes.
The other study used continuous glucose monitoring (CGM) data from 100 patients with type 2 diabetes and 60 with type 1 diabetes and found that glucose variability, defined as the standard deviation divided by the mean, significantly correlated with hypoglycemia in both groups of patients.
Hypoglycemia was defined as blood glucose below 3 mmol/L for at least 20 minutes and occurred in 24.0% of the type 2 diabetes patients and in 53.3% of those with type 1 during 4 to 6 days of monitoring.
Glycemic variability determined from self-monitored blood glucose (SMBG) also correlated with hypoglycemia risk, a point that presenter Suresh Rama Chandran (Singapore General Hospital) emphasized, given that CGM is often unavailable to patients. Area under the receiver-operating characteristic curve analysis showed that both CGM and SMBG glycemic variability were both highly predictive of hypoglycemia in type 1 diabetes patients; however, this was not the case for type 2 diabetes patients, with only CGM glycemic variability being strongly predictive. For these patients, the combination of CGM glycemic variability and HbA1c levels was more accurate.
And in the same session, Bernard Zinman (Mount Sinai Hospital, Toronto, Ontario, Canada) presented a post-hoc analysis of the LEADER trial, linking severe hypoglycemia to an increased cardiovascular and mortality risk. Severe hypoglycemia occurred in 2.4% of liraglutide-treated patients versus 3.3% of those in the placebo group, despite liraglutide treatment resulting in lower HbA1c levels.
Patients had a 2.2-fold increased risk for major adverse cardiovascular events (MACE) after a severe hypoglycemic episode, with the highest risk increase of 7.3-fold occurring in the 7 days after the episode and declining slowly thereafter. The same pattern was present, albeit less marked, for all-cause and non-cardiovascular mortality, with the overall risk for these outcomes being increased threefold.
Zinman noted, however, that the reduced hypoglycemia risk did not appear to account for the cardiovascular benefits of liraglutide previously shown in LEADER. And he agreed with a delegate who suggested that the relationship between hypoglycemia and outcomes could be a case of reverse causality, with ill, frail patients being vulnerable to both cardiovascular events and severe hypoglycemia.
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