The use of flash glucose monitoring significantly improves glycemic control in type 2 diabetes managed with basal bolus insulin therapy compared to self-monitoring of blood glucose: A prospective observational cohort study.

AIM: This prospective, observational cohort study aimed to measure HbA1c change over 3-6 months in type 2 diabetes managed with basal-bolus insulin and FreeStyle Libre® Flash Glucose Monitoring System (FSL) use compared to self-monitored blood glucose (SMBG). METHODS: Sixteen Italian hospitals enrolled patients with type 2 diabetes (n = 322, [109 FSL, 213 SMBG users]) using basal-bolus insulin therapy for ≥ 1 year, HbA1c 8.0-12.0% (64-108 mmol/mol), new to FSL use (<3 months) or continuing with SMBG (controls). Eligible FSL and SMBG users were matched (1:2 ratio) for baseline HbA1c (within ± 0.5%, recorded ≤ 3 months previously), study site and baseline data collection date. RESULTS: Overall, baseline HbA1c was 8.9 ± 0.8% (74 ± 9 mmol/mol), age 67.2 ± 10.0 years, BMI 30.5 ± 6.5 kg/m2 and insulin use duration 8.6 ± 6.6 years (mean ± SD), 56.2% were males. After 3-6 months, 234 complete cases (83 FSL, 151 SMBG users) demonstrated significantly reduced HbA1c for FSL use compared to SMBG (0.3% ± 0.12 [3 mmol/mol ± 1.3, (mean ± SE)], p = 0.0112). The difference remained statistically significant after adjusting for confounders. CONCLUSIONS: HbA1c significantly improved in basal-bolus treated type 2 diabetes after flash glucose monitoring use for 3-6 months compared to SMBG.

Peroxisome proliferator activated receptor-γ agonists protect oligodendrocyte progenitors against tumor necrosis factor-alpha-induced damage: Effects on mitochondrial functions and differentiation.

The activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) is known to exert anti-inflammatory and neuroprotective effects and PPAR-γ agonists are considered potential therapeutic agents in brain diseases including those affecting myelin. In demyelinating diseases such as multiple sclerosis (MS), inflammation is one of the causes of myelin and axonal damage. Oligodendrocyte (OL) differentiation is highly dependent on mitochondria, which are major targets of inflammatory insult. Here we show that PPAR-γ agonists protect OL progenitors against the maturational arrest induced by the inflammatory cytokine TNF-α by affecting mitochondrial functions. We demonstrate that the inhibition of OL differentiation by TNF-α is associated with i) increased mitochondrial superoxide production; ii) decreased mitochondrial membrane potential (mMP); and iii) decreased ADP-induced Ca(2+) oscillations, which we previously showed to be dependent on efficient mitochondria. The TNF-α effects were comparable to those of the mitochondrial toxin rotenone, further suggesting that TNF-α damage is mediated by mitochondrial function impairment. PPAR-γ agonists protected OL progenitors against the inhibitory activities of both TNF-α and rotenone on mMP, mitochondrial ROS production, Ca(2+) oscillations and OL differentiation. Finally, the PPAR-γ agonist pioglitazone increased the expression of PGC-1α (a mitochondrial biogenesis master regulator), UCP2 (a mitochondrial protein known to reduce ROS production), and cytochrome oxidase subunit COX1. These findings confirm the central role of mitochondria in OL differentiation and point to mitochondria as major targets of PPAR-γ agonist protection against TNF-α damage.

Glucose-induced insulin hypersecretion in lipid-infused healthy subjects is associated with a decrease in plasma norepinephrine concentration and urinary excretion.

We investigated the effect of a 48 h triglyceride infusion on the subsequent insulin secretion in response to glucose in healthy men. We measured the variations in plasma concentration and urinary excretion of catecholamines as an indirect estimation of sympathetic tone. For 48 h, 20 volunteers received a triglyceride/heparin or a saline solution, separated by a 1-month interval. At time 48 h, insulin secretion in response to glucose was investigated by a single iv glucose injection (0.5 g/kg(-1)) followed by an hyperglycemic clamp (10 mg.kg(-1).min(-1), during 50 min). The triglyceride infusion resulted in a 3-fold elevation in plasma free fatty acids and an increase in insulin and C-peptide plasma concentrations (1.5- and 2.5-fold, respectively, P < 0.05), compared with saline. At time 48 h of lipid infusion, plasma norepinephrine (NE) concentration and urinary excretion levels were lowered compared with saline (plasma NE: 0.65 +/- 0.08 vs. 0.42 +/- 0.06 ng/ml, P < 0.05; urinary excretion: 800 +/- 70 vs. 620 +/- 25 nmol/24 h, P < 0.05). In response to glucose loading, insulin and C-peptide plasma concentrations were higher in lipid compared with saline infusion (plasma insulin: 600 +/- 98 vs. 310 +/- 45 pM, P < 0.05; plasma C-peptide 3.5 +/- 0.2 vs. 1.7 +/- 0.2 nM, P < 0.05). In conclusion, in healthy subjects, a 48-h lipid infusion induces basal hyperinsulinemia and exaggerated insulin secretion in response to glucose which may be partly related to a decrease in sympathetic tone.

Influence of meal ingestion on insulin profiles following intraperitoneal delivery.

This study evaluated the effect of meal ingestion on intraperitoneal insulin absorption in type I diabetic patients with an implanted pump for long-term intraperitoneal insulin delivery. On four separate occasions, patients (n = 7) were administered 15 IU insulin as a 20-minute square-wave infusion using their implanted device; hypoglycemia was prevented by intravenous infusion of 10% dextrose at a variable rate. Two studies were performed during fasting conditions (n = 2 fasting tests) and two studies after the administration of an 800-kcal standard meal (n = 2 postprandial tests). An insulin peak of 630 +/- 545.4 pmol/L (mean +/- SD) in fasting tests and 696 +/- 420.5 pmol/L in postprandial tests was reached in the peripheral circulation after 45 +/- 11.7 and 45 +/- 14.7 minutes, respectively, with no significant difference between the two experimental conditions. Areas under the insulin curves were not significantly different in fasting and postprandial tests (51,500 +/- 34,278 v 50,916 +/- 20,558 pmol/L.min-1, respectively; NS). In type I diabetic patients receiving long-term intraperitoneal insulin therapy, the increase in splanchnic blood flow following ingestion of a standard meal does not accelerate the appearance of insulin in the peripheral circulation.

Insulin resistance in porphyria cutanea tarda.

It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

Studies on overnight insulin requirements and metabolic clearance rate of insulin in normal and diabetic man: relevance to the pathogenesis of the dawn phenomenon.

In order to assess whether the metabolic clearance of insulin changes overnight, 11 patients with Type 1 (insulin-dependent) diabetes and low insulin antibody titre, and 6 nondiabetic subjects were studied. In these studies insulin was always infused by a Harvard pump. Initially, the nocturnal insulin requirements were assessed in the diabetic patients by an overnight feedback insulin infusion to maintain euglycaemia. The insulin requirements decreased continuously after midnight to a nadir of 0.115 +/- 0.014 mU X kg-1 X min-1 at 04.30 hours, but after 05.00 hours the insulin requirements increased nearly 40 percent to a maximum of 0.16 +/- 0.012 mU X kg-1 X min-1 at 07.00 hours. To assess whether plasma insulin clearance changes overnight, the diabetic patients were studied on two different occasions, from 22.00-02.30 hours and from 04.00-08.30 hours. During each of these two studies insulin was infused in sequential steps of 90 min each at the rate of 0.13, 0.40 and 0.20 mU X kg-1 X min-1. Despite changes in plasma free insulin concentration, the metabolic clearance of insulin in the interval 22.00-02.30 hours (12.6 +/- 0.17 ml X kg-1 X min-1) was no different from that of the interval 04.00-08.30 hours (12.5 +/- 0.19 ml X kg-1 X min-1). The nondiabetic subjects were studied on two different occasions to assess whether the metabolic clearance of insulin changes overnight. Somatostatin (0.25 mg/h) and insulin (0.3 mU X kg-1 X min-1) were infused from 22.00-02.30 hours on one occasion, and from 04.00-08.30 hours on the other.(ABSTRACT TRUNCATED AT 250 WORDS)