Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised,placebo-controlled study

Aims/hypothesis

Liraglutide can modulate insulin secretion by directly stimulating beta cells or indirectly through weight loss and enhanced insulin sensitivity. Recently, we showed that liraglutide treatment in overweight individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) led to greater weight loss (?7.7% vs ?3.9%) and improvement in insulin resistance compared with placebo. The current study evaluates the effects on beta cell function of weight loss augmented by liraglutide compared with weight loss alone.

Methods

This was a parallel, randomised study conducted in a single academic centre. Both participants and study administrators were blinded to treatment assignment. Individuals who were 40–70 years old, overweight (BMI 27–40 kg/m²) and with prediabetes were randomised (via a computerised system) to receive liraglutide (n?=?35) or matching placebo (n?=?33), and 49 participants were analysed. All were instructed to follow an energy-restricted diet. Primary outcome was insulin secretory function, which was evaluated in response to graded infusions of glucose and day-long mixed meals.

Results

Liraglutide treatment (n?=?24) significantly (p?≤?0.03) increased the insulin secretion rate (% mean change [95% CI]; 21% [12, 31] vs ?4% [?11, 3]) and pancreatic beta cell sensitivity to intravenous glucose (229% [161, 276] vs ?0.5% (?15, 14]), and decreased insulin clearance rate (?3.5% [?11, 4] vs 8.2 [0.2, 16]) as compared with placebo (n?=?25). The liraglutide-treated group also had significantly (p?≤?0.03) lower day-long glucose (?8.2% [?11, ?6] vs ?0.1 [?3, 2]) and NEFA concentrations (?14 [?20, ?8] vs ?2.1 [?10, 6]) following mixed meals, whereas day-long insulin concentrations did not significantly differ as compared with placebo. In a multivariate regression analysis, weight loss was associated with a decrease in insulin secretion rate and day-long glucose and insulin concentrations in the placebo group (p?≤?0.05), but there was no association with weight loss in the liraglutide group. The most common side effect of liraglutide was nausea.

Conclusions/interpretation

A direct stimulatory effect on beta cell function was the predominant change in liraglutide-augmented weight loss. These changes appear to be independent of weight loss.

Trial registration

ClinicalTrials.gov NCT01784965

Funding

The study was funded by the ADA.     

Mediterranean diet and functional indicators among older adults in non-Mediterranean and Mediterranean countries

Background/Objectives

The Mediterranean diet (MEDDIET) has been shown to be related to longevity. This study aimed to determine the association between adherence to MEDDIET and physical function of older adults in the United-States and Israel.

Methods

Data from the US National Health and Nutrition Survey (NHANES) 1999–2002 and from the Israeli National Health and Nutrition Survey (MABAT ZAHAV) 2005–2006 were used. Participants with nutritional and functional data were included. Adherence to the MEDDIET was assessed by a 9-unit score (MDS).

Results

Among 2791 NHANES and 1786 MABAT ZAHAV participants, mean age=71.2y and 74.9y, 20% and 27% had low MDS (0–2), 66% and 62% had a medium score (3–5), and 14% and 11% had a high score (6–9), respectively. Higher MDS was associated with higher education and better lifestyle behaviors. Cognitive and physical functions were significantly better in NHANES and MABAT ZAHAV among the highest MDS. In NHANES, MDS (high vs. low) was associated with faster walking speed after adjusting for confounders in a logistic regression model [Odds Ratio (OR)=0.71, P=0.034, Cl 95% 0.511–0.974]. When cognitive function was added, the association was attenuated (OR=0.75, P=0.093, Cl 95% 0.540–1.049). In MABAT ZAHAV, in a logistic regression model adjusted among other to cognitive function, MDS (high vs. low) was associated with fewer disabilities (OR=0.51, P=0.029, Cl 95% 0.276–0.934).

Conclusions

Adherence to the MEDDIET is associated with better health characteristics and better functioning. Further cohort and intervention studies may shed light on temporal and causal relationships between MEDDIET and these parameters.     

Effectiveness of the Oka/GSK attenuated varicella vaccine for the prevention of chickenpox in clinical practice in Israel

BACKGROUND: The varicella Oka/Merck vaccine has been shown to be very effective in clinical practice; however, several recent studies reported reduced effectiveness. The varicella Oka/GSK vaccine (Varilrix; GlaxoSmithKline Biologicals), which has been subjected to fewer effectiveness studies, was licensed in Israel for voluntary use in 2000. This study was planned to estimate the effectiveness of the varicella Oka/GSK vaccine among children 1-5 years of age. METHODS: Recent reports of varicella were retrieved from the Tel Aviv Health District. Two age-matched control subjects who attended the same day-care center and/or resided in the same neighborhood and had not contracted varicella in the past were recruited for each varicella case. The parents of case and control subjects were interviewed regarding the history of varicella vaccination and the severity of illness. RESULTS: A total of 151 case subjects (mean age, 2.9 +/-1.1 years) and 298 control subjects (mean age, 3.0 +/-1.1 years) were recruited. Vaccination rates for case and control subjects were 6.6% and 38.3%, respectively (P < 0.001). Disease among vaccinated children was significantly milder, as measured by several indices, including parental perception of the illness, presence of fever, time until the lesions dried and days of day care missed. Vaccine effectiveness against varicella of any severity with these figures was 88% (95% confidence interval, 77-94%), and effectiveness against moderate/severe illness was 100%. CONCLUSIONS: Our data demonstrate that the varicella Oka/GSK vaccine used in clinical practice is highly effective in prevention of varicella (especially moderate/severe disease) among children, including those attending day-care centers.     

Development of a food frequency questionnaire (FFQ) for an elderly population based on a population survey

Older people have different eating patterns than their younger counterparts, although in most nutritional studies of older populations, food frequency questionnaires (FFQ) that were developed and validated for the general adult population are used. In this paper, we present the advantages of developing an FFQ for an older population based on a population survey. A random sample of the Negev's (Southern Israel) Jewish population > or = 35 y old was recruited and interviewed for their dietary intake using 24-h recalls. Foods eaten were aggregated into conceptually similar groups and entered into stepwise regression models to predict variation in nutrient intake. We interviewed 796 people age 35-64 y and 377 people > or = 65 y old for the study. Significantly more items were required to reach 80% between-person variability for zinc, magnesium, vitamin E and protein for the elderly compared with the younger age group. Portion sizes of most items consumed by the elderly were smaller compared with the Israeli Ministry of Health portion sizes booklet and the younger age group's intake estimates. The nutrient values assigned for each line based on a weighted mean of the intake of the elderly were different from those using the most frequently used item. The above findings highlight some of the advantages of developing an FFQ for an older population based on a population survey. Further studies are required to compare the validity of existing tools adapted for the elderly to those developed on the basis of population surveys.     

Understanding the gastrointestinal tract of the elderly to develop dietary solutions that prevent malnutrition

Although the prevalence of malnutrition in the old age is increasing worldwide a synthetic understanding of the impact of aging on the intake, digestion, and absorption of nutrients is still lacking. This review article aims at filling the gap in knowledge between the functional decline of the aging gastrointestinal tract (GIT) and the consequences of malnutrition on the health status of elderly. Changes in the aging GIT include the mechanical disintegration of food, gastrointestinal motor function, food transit, chemical food digestion, and functionality of the intestinal wall. These alterations progressively decrease the ability of the GIT to provide the aging organism with adequate levels of nutrients, what contributes to the development of malnutrition. Malnutrition, in turn, increases the risks for the development of a range of pathologies associated with most organ systems, in particular the nervous-, muscoskeletal-, cardiovascular-, immune-, and skin systems. In addition to psychological, economics, and societal factors, dietary solutions preventing malnutrition should thus propose dietary guidelines and food products that integrate knowledge on the functionality of the aging GIT and the nutritional status of the elderly. Achieving this goal will request the identification, validation, and correlative analysis of biomarkers of food intake, nutrient bioavailability, and malnutrition.     

Gender differences in factors associated with nutritional status of older medical patients

OBJECTIVES: To evaluate gender differences in nutritional risk of older people admitted to an acute-care general medical department, and identify gender-specific risk factors. DESIGN: Cross-sectional study. SETTING: Internal Medicine Department in an acute care, university-affiliated hospital in southern Israel. SUBJECTS: 204 cognitively intact patients aged 65 and over, admitted during a 12-month period to a general medical department. Measures of outcome: Evaluation included demographic and clinical data consisting of the sum of medical conditions and of prescribed medications, evaluation of nutritional status, cognitive status, depression assessment and functional ability. Statistical analyses were conducted to evaluate the gender specific risk factors for under-nutrition. RESULTS: 32.5% of the men and 48.1% of the women admitted to an internal medicine department were at risk for under-nutrition. Those at nutritional risk had a higher rate of depression, lower cognitive and physical ability, poorer reported health status and more diagnosed diseases. Nutritional risk for men was associated with higher depression score, longer hospitalization, and poor appetite. For women, nutritional risk was associated with lower functional status and more diagnosed diseases. In a multivariate analysis, being a female increased the risk of under-nutrition by 3.3 fold. CONCLUSION: Risk of under-nutrition is prevalent among older in-patients and is gender-related. Female inpatients are at markedly increased risk for under-nutrition. The mechanism of the gender discrepancy in factors related to nutritional deterioration is complex and poorly understood.     

The Association of Helicobacter pylori,Eradication, and Early Complications of Laparoscopic Sleeve Gastrectomy

Obesity Surgery - Laparoscopic sleeve gastrectomy (SG) is a common and effective bariatric surgery, with low postoperative complication rates. It is important to define modifiable risk factors for...