Obese Patients with Type 2 Diabetes on Conventional Versus Intensive Insulin Therapy: Efficacy of Low-Calorie Dietary Intervention

Introduction

The aim of this prospective study was to assess the results of a standard low-calorie dietary intervention (7.5 MJ/day) on body weight (BW) and the metabolic profile of obese patients with type 2 diabetes mellitus (T2DM) on intensive insulin therapy (IIT: 4 insulin injections/day) versus conventional insulin therapy (CIT: 2/3 insulin injections/day).

Methods

A total of 60 patients (n = 60, 23 males and 37 postmenopausal females) were recruited and categorized into two groups according to the scheme of insulin treatment. Thirty were on IIT (13 males and 17 females) and an equal number on CIT (10 males and 20 females). BW, body mass index (BMI), HbA1c, and metabolic parameters were compared at 6 and 12 months after baseline.

Results

Significant reductions were observed in the BW, BMI, HbA1c (p ≤ 0.001 for all) and cholesterol (p ≤ 0.05) at 6 months post-intervention. At 1 year, median BW reduction was 4.5 kg (3.3, 5.8) for patients on IIT and 4.8 kg (3.6, 7.0) for those on CIT. The 12-month dietary intervention increased prevalence of normoglycemia in the IIT group and reduced the prevalence of obesity prevalence among the CIT participants (all p < 0.001). CIT patients with BW reduction ≥5.0% demonstrated 11-fold greater chances of being normoglycemic (odds ratio 11.3, 95% CI 1.1–110.5). BW reduction ≥7.0% was associated with CIT, being overweight, and having normal HDLc, LDLc, and cholesterol levels. A reduction in BW between 5.0% and 6.9% was associated with IIT, normoglycemia, and obesity.

Conclusion

A 12-month 1800-kcal dietary intervention achieved significant BW and HbA1c reductions irrespectively of insulin regimen. CIT was associated with BW reduction greater than 8.0%, whereas IIT was associated with higher rates of normoglycemia.

     

Neural stem/progenitor cells differentiate into oligodendrocytes,reduce inflammation,and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury

The central nervous system has limited capacity for regeneration after traumatic injury. Transplantation of neural stem/progenitor cells (NPCs) has been proposed as a potential therapeutic approach while insulin‐like growth factor I (IGF‐I) has neuroprotective properties following various experimental insults to the nervous system. We have previously shown that NPCs transduced with a lentiviral vector for IGF‐I overexpression have an enhanced ability to give rise to neurons in vitro but also in vivo, upon transplantation in a mouse model of temporal lobe epilepsy. Here we studied the regenerative potential of NPCs, IGF‐I‐transduced or not, in a mouse model of hippocampal mechanical injury. NPC transplantation, with or without IGF‐I transduction, rescued the injury‐induced spatial learning deficits as revealed in the Morris Water Maze. Moreover, it had beneficial effects on the host tissue by reducing astroglial activation and microglial/macrophage accumulation while enhancing generation of endogenous oligodendrocyte precursor cells. One or two months after transplantation the grafted NPCs had migrated towards the lesion site and in the neighboring myelin‐rich regions. Transplanted cells differentiated toward the oligodendroglial, but not the neuronal or astrocytic lineages, expressing the early and late oligodendrocyte markers NG2, Olig2, and CNPase. The newly generated oligodendrocytes reached maturity and formed myelin internodes. Our current and previous observations illustrate the high plasticity of transplanted NPCs which can acquire injury‐dependent phenotypes within the host CNS, supporting the fact that reciprocal interactions between transplanted cells and the host tissue are an important factor to be considered when designing prospective cell‐based therapies for CNS degenerative conditions. GLIA 2016;64:763–779     

Kikuchi’s lymphadenopathy: a relatively rare but important cause of lymphadenopathy in Greece, potentially associated with the antiphospholipid syndrome

Kikuchi-Fujimoto disease is a form of reactive lymphadenopathy, which was firstly described in Japan, but is uncommon in the Western world. We retrospectively reviewed the medical records of nine cases of adult or adolescent Kikuchi’s disease diagnosed in a single Haematology Unit in Athens, Greece between 1990 and 2006. The median age of the patients was 25 years (14–40) and 8/9 were females. All patients presented with cervical lymphadenopathy sparing the supraclavicular fossa; one had associated axillary lymphadenopathy, seven had fever and two were asymptomatic. The median duration of lymphadenopathy before presentation was 30 days (10–45). Just palpable splenomegaly was recorded in three patients. The median value of the maximal lymph node diameter was 2 cm (1–5) and only 1/9 had nodes >2 cm in their largest diameter. Lymphadenopathy was tender in two patients; hard nodes were observed in three patients. The median leukocyte count was 4.7 × 10⁹/l (2.2–4.9) with a normal differential in 7/9 patients. No infectious agent could be demonstrated. One patient had clinical and laboratory evidence of primary antiphospholipid syndrome (APLS). In conclusion, Kikuchi’s disease represents a rare but important diagnostic possibility for patients presenting with lymphadenopathy in Greece and other western countries. In this setting, autoimmune disorders, mainly lupus and APLS, should be considered and excluded by the appropriate laboratory work-up.     

Ecstasy (MDMA)-induced hyponatraemia is associated with genetic variants in CYP2D6 and COMT

We hypothesised that genetically determined poor metabolism of 3,4-methylene dioxymetamphetamine (MDMA) due either to the presence of CYP2D6 genotypes giving absent or low CYP2D6 enzyme activity, or a COMT genotype predicting low COMT enzyme activity would be associated with a greater degree of MDMA-induced reduction in plasma sodium and osmolality than other genotypes at these genes following consumption of 'ecstasy' tablets by clubbers. Of the 48 subjects who returned to the test site post-clubbing, 30 provided samples for measurement of vasopressin (AVP), plasma sodium, urea and plasma and urine osmolality. Genotyping was performed for functional variants in CYP2D6 (n = 29) and COMT (Val158Met, n = 30). In subjects with urinary MDMA detected post-clubbing, there was a significant association between change in plasma osmolality (p = 0.009) and in plasma sodium (p = 0.012) and CYP2D6 genotypic category. Individuals with the low-activity but readily inhibitable CYP2D6 extensive metaboliser/intermediate metaboliser (EM/IM) genotype showed greater reductions in these measures than all other CYP2D6 genotypic categories. COMT low-activity genotypes (Met/Met and Val/Met) were also significantly associated with reductions in plasma osmolality (p = 0.028) and in plasma sodium (p = 0.003). On conservative Bonferroni correction for two independent genes, the CYP2D6 and COMT plasma sodium findings remain significant. The relatively high frequency of the low-activity CYP2D6 and COMT genotypes in the population warrants further attention, since consumption of free water following ingestion of MDMA in these individuals may trigger dilutational hyponatraemia and increased risk of syndrome of inappropriate antidiuretic hormone secretion.     

Containment of an outbreak of KPC-3-producing Klebsiella pneumoniae in Italy

From March 2009 to May 2009, 24 carbapenem-resistant Klebsiella pneumoniae isolates were recovered from 16 patients hospitalized in an Italian intensive care unit (ICU). All isolates contained KPC-3 carbapenemase and belonged to a single pulsed-field gel electrophoresis (PFGE) clone of multilocus sequence type 258 (designated as ST258). A multimodal infection control program was put into effect, and the spread of the KPC-3-producing K. pneumoniae clone was ultimately controlled without closing the ICU to new admissions. Reinforced infection control measures and strict monitoring of the staff adherence were necessary for the control of the outbreak.     

A 6-month follow-up of intermittent levosimendan administration effect on systolic function, specific activity questionnaire, and arrhythmia in advanced heart failure

BackgroundLevosimendan (LS) improves cardiac contractility without increasing myocardial oxygen demand. We administrated LS on a monthly intermittent 24-hour protocol and evaluated the clinical effect after 6 months in a randomized, open, prospective study.Methods and ResultsFifty patients (age 45–65 years) with LV systolic dysfunction and New York Heart Association (NYHA) III or IV were randomized in 2 groups. LS group (n = 25) was compared with a control group (n = 25) matched for sex, age, and NYHA class. LS was given monthly on a 24-hour intravenous protocol for 6 months. Patients were evaluated by specific activity questionnaire (SAQ) and echocardiography (ECHO) before and 3 to 5 days after last drug administration, whereas 24-hour Holter recording was performed before and during last drug administration. Patients in LS and control group had same baseline SAQ, ECHO, and Holter parameters. At the end of the study, a larger proportion of patients in the levosimendan group reported improvement in symptoms (dyspnea and fatigue) (65% versus 20% in controls, P < .01). After 6 months, the LS group had a significant increase in LV ejection fraction versus controls (28 ± 7 versus 21 ± 4 %, P = .003), LV shortening fraction (15 ± 3 versus 11 ± 3 %, P = .006) and a decrease in mitral regurgitation (1.5 ± 0.8 versus 2.7 ± 0.6, P = .0001). There was no increase in supraventricular or ventricular beats or supraventricular tachycardia and VT episodes in LS group, compared with controls. Two patients from the LS group died in the 6-month follow-up period, compared with 8 patients in the control group (8% versus 32%, P < .05).ConclusionsA 6-month intermittent LS treatment in patients with decompensated advanced heart failure improved symptoms and LV systolic function.