Optimized basal-bolus therapy using a fixed mixture of 75% lispro and 25% NPL insulin in type 1 diabetes patients: no favorable effects on glycemic control, physiological responses to hypoglycemia, well-being, or treatment satisfaction.

Abstract

RESEARCH DESIGN AND METHODS -We studied 35 type 1 diabetes patients.After an 8-to 10-week lead-in period, patients were randomized to HM or human regular insulin therapy for 12-14 weeks. During the lead-in and treatment periods, HbA 1c levels and hypoglycemic frequencies were measured, and patients completed the Well-Being Questionnaire and the Diabetes Treatment Satisfaction Questionnaire. In 19 patients, responses to hypoglycemia were tested during stepped euglycemic-hypoglycemic clamps.RESULTS -HM treatment improved postprandial glycemia but had no effect on HbA 1c , frequency of hypoglycemia, well-being, or treatment satisfaction. During experimental hypoglycemia, HM therapy was associated with a slightly lower total adrenaline response and a higher autonomic symptom threshold (i.e., the autonomic symptom response occurred at a lower blood glucose level) than human regular insulin therapy. We speculate that this effect resulted from an accumulation of insulin during the night.CONCLUSIONS -Multiple injection therapy with HM rather than human regular insulin before meals does not offer advantages regarding glycemic control, frequency of hypoglycemia, well-being, or treatment satisfaction. In addition, this regimen causes an attenuation of the adrenaline and autonomic symptom responses to hypoglycemia. E m e r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s

Interventions That Restore Awareness of Hypoglycemia in Adults With Type 1 Diabetes: A Systematic Review and Meta-analysis

“…There were no significant changes in glycemic control in the three lispro studies (64,65,67). HbA 1c was lower at the end of the treatment period in the split-NPH dosing (66).…”

“…The study on propranolol reported increased sweating during hypoglycemia with propranolol (68). There were no significant differences in counterregulatory hormones responses between lispro and SI (64) or SI before meals and NPH at bedtime versus the premix formulation of lispro, HM insulin (75% lispro and 25% neutral protamine lispro [NPL]) with meals and NPL at bedtime (67). There was, however, a higher peak plasma epinephrine response when NPH was delivered separately at bedtime compared with a combined SI and NPH with dinner (66).…”

“…SH did not occur in three of these studies (64,66,68); two had no statistically significant change in SH rates between study arms (65,67). There was no consistent finding in changes in hypoglycemia symptom scores during hypoglycemic clamp studies between comparator arms in the insulin studies (64)(65)(66)(67). The study on propranolol reported increased sweating during hypoglycemia with propranolol (68).…”

“…Five studies were identified, all of which were conducted more than 10 years ago. Four studies compared short-acting and long-acting analog insulin against conventional soluble (SI) or NPH insulin (64)(65)(66)(67). One noninsulin study was identified, investigating propranolol to restore HA (68).…”

Microvascular Disease in Type 1 Diabetes Alters Brain Activation

“…The left hand was placed in the hand box at 55°C (serie 134410, Kobold TD 1300 D), resulting in an oxygen saturation in the venous blood during euglycemia and hypoglycemia of 97%. During scanning, plasma glucose was kept at a euglycemic level (72-108 mg/dl) using the hyperinsulinemic-euglycemic clamp technique as described previously (19,20). Hypoglycemia (ϳ45 mg/dl) was reached by a one-step decrease of blood glucose.…”