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Pharmacological and Surgical Interventions to Improve Brain Insulin Resistance
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Linus Haberbosch, Lukas Maurer, Reiner Jumpertz-von Schwartzenberg
Of the peripheral insulins and insulin analogues used in the therapy of type 2 diabetes, most have not shown any effect on central insulin resistance, with the notable exception of insulin detemir. This insulin analogue was shown to increase cerebrocortical beta activity in obese subjects during an euglycemic clamp similar to lean subjects, an effect not found for the human insulin applied in the control group (37). Insulin detemir, applied peripherally, is characterized by a higher peak concentration in cerebrospinal fluid (CSF) and remained elevated for a longer period compared to NPH insulin, possibly on account of its lipophilic nature (38, 39). There is also data suggesting a reduced food intake/weight gain effect of insulin detemir (33, 40), further hinting towards a possible effect on central insulin signaling. While peripheral insulin effects on central insulin sensitivity should be further investigated, its therapeutic use is currently limited by the high doses needed to ensure adequate CSF levels and the resulting increased risk of hypoglycemia. Therefore, recent studies have concentrated on alternative application routes of insulin possibly capable of bypassing the blood-brain barrier (36, 41).
Diabetes in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
A number of insulin analogs have come on the market. Insulin lispro and insulin aspart are short-acting insulins, with a more rapid onset of action than that of regular insulin. Each differs from natural human insulin by a single amino acid. They can be given immediately before a meal, which increases flexibility of lifestyle. Insulin lispro does not cross the placenta to any great extent (59), and insulin aspart appears to have similar properties (60,61). Insulin glargine and insulin detemir are long-acting insulins with at least 24 hours of duration of action. Their absorption curve appears to be flat with no peak, and so their use can mimic basal insulin production by the pancreas or that of a continuous subcutaneous insulin infusion pump. In isolated placental perfusion models, insulin glargine at therapeutic concentrations on the maternal side did not reach detectable levels in the fetus, and even at very high levels, the rate of transfer was low (62). No published studies regarding transplacental passage of insulin detemir were found. If long-acting insulin analogs are used in pregnancy, insulin glargine is preferred to insulin detemir at the present time.
Immunosuppressants, rheumatic and gastrointestinal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
In children, intermediate- or long-acting insulin preparations are injected once or twice daily to mimic basal insulin production by the healthy pancreas. When given at bedtime as part of a multiple-injection regime, the peak of action of intermediate preparations, such as isophane insulin, occurs in the early part of the night, when insulin requirements are low. Conversely, the actions are wearing off by dawn when insulin requirements rise and may result in morning hyperglycaemia. Increasing the dose of bedtime isophane to control morning blood glucose may exacerbate lengthy periods of nocturnal hypoglycaemia, and may be compounded by ongoing absorption of soluble insulin injected with the evening meal. The long-acting insulin analogues, which have more of a peakless profile, may reduce this problem. Substitution of insulin glargine and a rapid-acting insulin analogue for a regime of isophane and soluble insulins leads to reductions in nocturnal hypoglycaemia in adolescents with T1DM [8]. Preliminary data in adults indicate that substitution of insulin detemir for isophane may reduce the risk of hypoglycaemia [11], however there is as yet no published data pertaining to rates of hypoglycaemia in children treated with insulin detemir.
Advances in pharmacological treatment of type 1 diabetes during pregnancy
Published in Expert Opinion on Pharmacotherapy, 2019
Angelo Maria Patti, Rosaria Vincenza Giglio, Kalliopi Pafili, Manfredi Rizzo, Nikolaos Papanas
Soluble human insulin and NPH have long been safely used [12,15,16]. The newer quick-acting insulin analogues aspart and lispro are also safe and are very widely used in combination with basal insulins in the MDI regimen [12,31,32]. Aspart and lispro may offer some benefits in terms of postprandial glucose control and preventing severe hypoglycaemia [12,31,32]. The long-acting insulin analogues glargine and detemir have not yet been explicitly approved for pregnancy in T1DM [12,31,32]. Glycaemic control and pregnancy outcomes were comparable in women using insulin detemir or glargine, except for a lower prevalence of large for gestational age infants in women on glargine. A trial (N = 162 women) compared insulin Detemir with NPH insulin: there were three cases of major foetal anomalies in the insulin Detemir group and one in the NPH insulin group, with no clear difference between the groups (RR: 3.15, 95% CI: 0.33–29.67); the estimated HbA1c at 36 gestation weeks was 6.27% for IDet and 6.33% for NPH. IDet was non-inferior to NPH [33]. In another trial of detemir vs. glargine, HbA1c was comparable at 8 weeks (6.6% vs. 6.8%, p = 0.15) and at 33 weeks (6.1% vs. 6.2%, p = 0.38) [34]. The use of both long-acting insulin analogues during pregnancy seems safe [34].
Influence of one-day diabetes mellitus clinic management on blood glucose control and prognosis in patients with gestational diabetes mellitus
Published in Gynecological Endocrinology, 2022
Wei Wang, Yan-Min Cao, Na-Na Cai, Qing Guo, You-Xia Zhou, Jie Liu, Peng Zhang
The application rate of insulin therapy in the one-day DM clinic group was higher than in the control group, and the difference was statistically significant (p < .05). There was no statistically significant difference between the two groups of patients concerning the number of cases using insulin aspart + insulin detemir and insulin aspart alone (p > .05). In the case of the use of insulin detemir alone, there existed a statistically significant difference, and the number of cases with the use of insulin detemir alone was higher in the one-day DM clinic group than in the control group (p < 0.05) (Table 1).
Efficacy and safety of insulin detemir versus glargine in patients with diabetes: a systematic review and meta-analysis
Published in Expert Review of Clinical Pharmacology, 2022
Soheila Rezaei, Ali Taheri, Saeed Taheri, Sara Kasirzadeh, Behzad Fatemi, Mende M Sorato
Consistent with ADA recommendations, insulin detemir was administered once a day or in divided doses twice a day in the included studies, while insulin glargine was only administered once a day. Only insulin glargine 100 IU/mL was used in 11 of the 12 included studies. In the study by Meneghini et al. [20], patients received either insulin glargine 300 IU/mL (1,651 patients), insulin glargine 100 IU/mL (1,081 patients), or insulin detemir (572 patients). In this study, insulin glargine 300 IU/mL and 100 IU/mL were administered once daily, at equivalent initial doses.