Insulin therapy in type 2 diabetes : Initiation, impact on liver fat, role of combination therapy with glitazones or glindes
Year: 2014
Type: dissertation
Abstract: Aims: The aims of the present studies were to understand the role of the liver in regulating the response to anti-hyperglycemic treatment, and to find ways to optimize basal insulin therapy in patients with type 2 diabetes. We determined whether i) insulin therapy changes liver fat content (LFAT) or hepatic insulin sensitivity (I), ii) a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone decreases insulin requirements, hepatic insulin resistance and LFAT in patients using high doses of insulin (II), iii) adding nateglinide decreases postprandial glucose excursions (PPGEs) in patients treated with the combination of basal insulin and metformin (MET) (III), iv) insulin can be started in groups as well as individually (IV). Subject and methods: Patients with type 2 diabetes participated in the studies I-IV. In study I, 14 patients treated with MET alone were studied before and after (7 months) addition of basal insulin. In study II, 14 patients who were poorly controlled, i.e. HbA1c 8.9 ± 0.4% despite of using high doses of insulin (1.98 ± 0.2 IU/kg) and MET were studied before and after (8 months) the addition of rosiglitazone (8mg/day). LFAT content (proton magnetic resonance spectroscopy, 1H-MRS), fat distribution (magnetic resonance imaging, MRI), fat-free mass and fat mass, whole body and hepatic insulin sensitivity (6-h euglycemic hyperinsulinemic clamp [insulin 0.3 mU/kg∙min] combined with infusion of [3-3H]-glucose), and substrate oxidation rates (indirect calorimetry) were measured. Study III was an investigator-initiated, double-blind, randomized, parallel-group study in the five centers. 88 patients treated with basal insulin and MET, after 24-week period to optimize glucose control, were randomized to receive either nateglinide (120 mg three times daily) or placebo for 24 weeks. HbA1c, postprandial glucose excursions, diurnal glucose profiles and the episodes of hypoglycemia were recorded. Study IV was a randomized (1:1), multicenter, two-arm, parallel design study with run-in phase (3-14 weeks). 121 insulin-naive patients were randomized to initiate basal insulin either in groups of 4-8 or individually, using the same personnel and education program for 24 weeks. Patients self-adjusted the insulin dose. HbA1c, the episodes of hypoglycemia, treatment satisfaction, and time spent on patient education were measured. Results: Insulin therapy decreased significantly LFAT (-20%), and enhanced hepatic insulin sensitivity. Insulin requirements correlated with LFAT. The change in LFAT was significantly correlated with that in hepatic insulin sensitivity. Rosiglitazone significantly improved glycemic control, decreased liver fat (by 46%) and insulin requirements (by 41%), and enhanced hepatic insulin sensitivity. The change in liver fat correlated with the decrease in HbA1c, and improvement in hepatic insulin sensitivity. Nateglinide added to basal insulin and MET slightly but significantly decreased HbA1c due to a decrease in postprandial glucose as compared to placebo. The episodes of symptomatic hypoglycemia were higher in the nateglide group compared to placebo group (p PIENEMPI 0.05). In the study comparing methods to initiate basal insulin, HbA1c decreased from 8.7 ± 0.2 to 6.9 ± 0.1% and from 8.8 ± 0.2 to 6.8 ± 0.1% in the individually educated patients and in the education in groups, (not significant [NS]). Insulin doses and frequency of hypoglycemia were similar in both groups. Diabetes treatment satisfaction improved similarly in both groups. The total time spent in initiating insulin in groups was 48% less than in those treated individually. Conclusions: In conclusion, insulin therapy has favorable effects on the liver as it reduces LFAT and improves hepatic insulin sensitivity. Rosiglitazone decreases LFAT, enhances hepatic insulin sensitivity in diabetic patients using high doses of insulin. Addition of a short-acting insulin secretagogue to basal insulin with MET slightly but significantly improves postprandial hyperglycemia. Similar glycemic control and treatment satisfaction can be achieved by initiating insulin in groups and individually but half less time was spent on patient education in groups.
Source: Työväentutkimus Vuosikirja
Author: Leena Juurinen
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1605680137