Differential Effects of Human and Animal Insulin on the Responses to Hypoglycemia in Elderly Patients With NIDDM

Abstract

Recent studies suggest that insulin-dependent diabetes mellitus patients switched from animal to human insulin may have decreased awareness of hypoglycemic warning symptoms. The risk of severe or fatal hypoglycemia associated with the treatment of diabetes increases with age. We conducted these studies to determine if awareness of hypoglycemic warning symptoms was greater with animal than with human insulin in elderly patients with diabetes. Nonobese elderly patients with non-insulin-dependent diabetes mellitus (NIDDM) (n = 13; age, 74 +/- 1 years; body mass index, 26.6 +/- 0.7 kg/m2) underwent paired hyperinsulinemic glucose clamp studies (insulin infusion rate 60 mU.m-2.min) in random order. In one study, regular human insulin was infused, and in the other study, regular beef/pork insulin was infused. In all studies, plasma glucose was decreased from fasting levels to 5 mmol/l during the first 60 min and was then allowed to fall to 4.4, 3.8, 3.3, and 2.8 mmol/l in each subsequent hour. Subjects were blinded as to which study they were undergoing. In each study, a hypoglycemic symptom checklist was administered, and counterregulatory hormones were measured every 15 min. Neuropsychological tests were performed every hour. Counterregulatory hormone responses to the two insulin preparations were similar. Autonomic (P < 0.05) and neuroglycopenic (P < 0.01) symptom scores were significantly higher during the beef/pork insulin studies. The responses on the neuropsychological tests were not significantly different. We conclude that beef/pork insulin results in greater awareness of hypoglycemic warning symptoms than does human insulin in elderly patients with NIDDM.

Hypoglycaemia induced by exogenous insulin –‘human’ and animal insulin compared

“…Significant increases in the frequency of hypoglycaemia and/or reduced symptoms of hypoglycaemia were reported in seven of the 37 double‐blind RCTs. Two of these reports[17–18] (Table 1) were population‐based and three[20–21,23] (Table 3) were laboratory based studies involving patients who had not previously reported impaired awareness. All five of these were carried out in subjects with long‐standing diabetes or on intensified therapy.…”

“…All but one[61] provided data on hypoglycaemic events, this study simply reporting no events during the investigation. Four studies found no differences in the frequency of hypoglycaemia[2–64]. Two studies reported a statistically insignificantly increased frequency of hypoglycaemia in subjects on ‘human’ insulin as compared to those on insulin of animal origin[65–66].…”

“…Nineteen publications[6–92] compare a period of animal insulin treatment to one of ‘human’ insulin treatment in the same subject. Nine of these studies[75–77,81–83,85–86,88–91] reported no difference between insulin species while a further three[78–79,92] found fewer hypogycaemic episodes with ‘human’ insulin and/or greater awareness of hypoglycaemia.…”

Glucose counterregulation in Type 2 diabetes mellitus

“…All papers concerning glucose counterregulatory hormone responses to hypoglycaemia in Type 2 DM were regarded eligible for evaluation in this review. We were able to retrieve 16 research articles [23–37,39], the characteristics of which are shown in Table 2. From the study by Polonsky et al .…”

“…Finally, hypoglycaemia associated with oral agents, particularly glibenclamide and chlorpropamide [19–21], may be very persistent and occasionally lethal [22]. Relatively little is known about the integrity of counterregulation in patients with Type 2 DM and its role in the vulnerability to hypoglycaemia [23–37]. Since tight metabolic control is being increasingly advocated in Type 2 DM [38], it is important to understand whether impaired glucose counterregulation might limit its implementation.…”