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Accurate bolus insulin doses require calculations based on (1) current blood glucose, (2) target blood glucose, (3) carbohydrate-to-insulin ratios, (4) total grams of carbohydrate in meals, and (5) insulin sensitivity factors. Patients may often forego these calculations for insulin doses based on empirical estimates. A bolus calculator (Medtronic MiniMed) uses these five parameters to generate a recommended bolus insulin dose. This study provides the evidence that a hand-held bolus calculator is effective in controlling postprandial blood glucose. Subjects (n = 49) with Type 1 diabetes and experienced with continuous subcutaneous insulin infusion therapy were randomized to begin one of two bolus dosing methods. After 7 days, subjects crossed over to the alternate method. Prior to entering the Bolus Calculator period, physicians established patients' bolus parameters and programmed them into a personal digital assistant (PDA). Subjects used the PDA to obtain recommended pre-meal insulin bolus doses. During the Standard Bolus period, significantly more correction boluses were administered to curtail postprandial hyperglycemia (p = 0.008) and more supplemental carbohydrate was consumed to raise low blood glucose (p = 0.046). Similar values were observed between the two bolus dosing methods in average deviation of 2-h postprandial blood glucose. Subjects reported that the bolus calculator was easy to use and that they were confident in the bolus doses suggested by the device. These results confirm that bolus insulin doses computed by a bolus calculator, compared with standard bolus techniques, achieve target postprandial blood glucose but with fewer correction boluses and supplemental carbohydrate. A bolus calculator, which can be integrated into insulin pump software, may help patients to more accurately meet prandial insulin dosage requirements, improve postprandial glycemic excursions, and achieve optimal glycemic control.

Insulin analogues have been engineered to enhance desired molecular properties without altering immunogenicity. The majority of insulin pharmacology studies are conducted in healthy volunteers and patients with type 1 diabetes. At present, there are more patients with type 2 than type 1 diabetes receiving insulin treatment. As the responsibility for initiating insulin therapy in these patients continues to shift to primary care, it will be important for general practitioners to understand the different pharmacological properties of insulin preparations in patients with type 2 diabetes, so that treatment can be adapted to meet patients’ physiological and lifestyle requirements. The purpose of this review is to summarize pharmacological studies of insulin analogues in patients with type 2 diabetes. Faster onset of action of rapid acting insulin analogues has improved postprandial glycaemic control. Biphasic insulin analogues are associated with a lower incidence of nocturnal hypoglycaemia compared with human biphasic preparations and allow for intensification from once to twice or thrice daily dosing. More predictable glycaemic-lowering profiles of the insulin analogues have also led to reductions in nocturnal hypoglycaemia, particularly comparing long-acting insulin analogues with protaminated human insulin. Enhancing insulin self-association and reversible binding with albumin has led to further reductions in variability. However, improvements can still be made. Effective once daily clinical dosing of long-acting insulin analogues is not possible in all patients. In addition, the protaminated component of biphasic insulin analogues do not provide the duration of action or profile for physiological basal insulin replacement and neither insulin glargine nor insulin detemir are suitable for mixing with other insulin analogues as this would substantially alter their pharmacokinetic properties. Enhancing the pharmacological predictability and extending the duration of action could simplify insulin titration and further reduce the incidence of hypoglycaemia.

OBJECTIVETo evaluate efficacy and tolerability of a co-formulation of insulin degludec and insulin aspart (IDegAsp) with insulin aspart (IAsp) at other meals compared with basal-bolus therapy using insulin detemir (IDet) and IAsp.RESEARCH DESIGN AND METHODSAdults (n = 548) with type 1 diabetes (A1C 7.0–10.0%; BMI ≤35.0 kg/m2) were randomized 2:1 in a 26-week, multinational, parallel-group, treat-to-target trial to IDegAsp or IDet. IDegAsp was given with a meal, and IDet was given in the evening, with a second (breakfast) dose added if needed.RESULTSNon-inferiority for IDegAsp versus IDet was confirmed; A1C improved by 0.75% with IDegAsp and 0.70% with IDet to 7.6% in both groups (estimated treatment difference IDegAsp − IDet: –0.05% [95% CI –0.18 to 0.08]). There was no statistically significant difference between IDegAsp and IDet in the rates of severe hypoglycemia (0.33 and 0.42 episodes/patient-year, respectively) or overall confirmed (plasma glucose <3.1 mmol/L) hypoglycemia (39.17 and 44.34 episodes/patient-year, respectively). Nocturnal confirmed hypoglycemia rate was 37% lower with IDegAsp than IDet (3.71 vs. 5.72 episodes/patient-year, P < 0.05). Weight gain was 2.3 and 1.3 kg with IDegAsp and IDet, respectively (P < 0.05). Total insulin dose was 13% lower in the IDegAsp group (P < 0.0001). No treatment differences were detected in Health-Related Quality of Life, laboratory measurements, physical examination, vital signs, electrocardiograms, fundoscopy, or adverse events.CONCLUSIONSIDegAsp in basal-bolus therapy with IAsp at additional mealtimes improves overall glycemic control and was non-inferior to IDet, with a reduced risk of nocturnal hypoglycemia and fewer injections in comparison with IDet + IAsp basal-bolus therapy.