A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus

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Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: a meta-analysis of randomized controlled trials

Introduction: Chromium is an essential trace mineral for carbohydrate and lipid metabolism, which is currently prescribed to control diabetes mellitus. Results of previous systematic reviews and meta-analyses of chromium supplementation and metabolic profiles in diabetes have been inconsistent. Aim: The objective of this meta-analysis was to assess the effects on metabolic profiles and safety of chromium supplementation in type 2 diabetes mellitus and cholesterol. Methods: Literature searches in PubMed, Scopus and Web of Science were made by use of related terms-keywords and randomized clinical trials during the period of 2000-2014. Results: Thirteen trials fulfilled the inclusion criteria and were included in this systematic review. Total doses of Cr supplementation and brewer's yeast ranged from 42 to 1,000 µg/day, and duration of supplementation ranged from 30 to 120 days. The analysis indicated that there was a significant effect of chromium supplementation in diabetics on fasting plasma glucose with a weighted average effect size of -29.26 mg/dL, p = 0.01, CI 95% = -52.4 to -6.09; and on total cholesterol with a weighted average effect size of -6.7 mg/dL, p = 0.01, CI 95% = -11.88 to -1.53. Conclusions: The available evidence suggests favourable effects of chromium supplementation on glycaemic control in patients with diabetes. Chromium supplementation may additionally improve total cholesterol levels.

The contribution of workplace characteristics to the risk of Type 2 Diabetes

Diabetes has a significant economic impact on individuals, families, health systems, and countries [1]. In 2010 it was estimated that the global health expenditure on diabetes was US376 billion (€292 billion), equating to 12% of health expenditure and US1330 (€1031) per person [2]. A separate estimate in 2010 reported that diabetes cost the US US174 billion (€135 billion), with US58 billion (€45 billion) in indirect costs equating to over US2000 (€1551) on average per person with diabetes [3]. The World Health Organization estimates that between 2005 and 2030 the proportion of deaths caused by diabetes will double and global health expenditures associated with diabetes are expected to reach US490 billion (€380 billion) [1,2]. In 2003, it was estimated that diabetes cost Australia AUS6 billion (US6 billion, €5 billion), with AUS21 million (US22 million, €17 million) in indirect costs such as lost workdays and lost productivity equating to approximately AUS35 (US35, €28) per person with diabetes [4].

An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor alogliptin used for the treatment of type 2 diabetes mellitus.

Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor that is a class of relatively new oral hypoglycaemic drugs used in patients with type 2 diabetes (T2DM), can be used as monotherapy or in combination with other anti-diabetic agents, including metformin, pioglitazone, sulfonylureas and insulin with a considerable therapeutic effect. Alogliptin exhibits favorable pharmacokinetic and pharmacodynamic profiles in humans. Alogliptin is mainly metabolized by cytochrome P450 (CYP2D6) and CYP3A4. Dose reduction is recommended for patients with moderate or worse renal impairment. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections and headache. Hypoglycaemia is seen in about 1.5% of the T2DM patients. Rare but severe adverse reactions such as acute pancreatitis, serious hypersensitivity including anaphylaxis, angioedema and severe cutaneous reactions such as Stevens-Johnson syndrome have been reported from post-marketing monitoring. Pharmacokinetic interactions have not been observed between alogliptin and other drugs including glyburide, metformin, pioglitazone, insulin and warfarin. The present review aimed to update the clinical information on pharmacodynamics, pharmacokinetics, adverse effects and drug interactions, and to discuss the future directions of alogliptin.

Willingness to initiate insulin among adults with type 2 diabetes in Australian primary care: results from the Stepping Up Study

AIMS: To determine 'hypothetical willingness' to initiate insulin, and identify associated factors, among adults with type 2 diabetes (T2DM) in primary care for whom insulin is clinically indicated.

METHODS: Eligible participants were adults with T2DM with an HbA1c ≥7.5% (58mmol/mol) and prescribed maximum oral hypoglycaemic agents. A total of 261 participants were recruited from 74 Victorian general practices: mean age 62±10 years; 39% (n=103) women; diabetes duration 10±6 years; HbA1c 9.0±1.3% (75±14mmol/mol). Data collected by the Stepping Up Study: demographic and clinical characteristics, 'willingness' to initiate insulin, insulin appraisals, depressive symptoms, and diabetes-related distress. A multinomial regression investigated predictors of 'willingness'.

RESULTS: Nineteen percent (n=50) were 'very willing' to initiate insulin, if recommended. The final regression model (R(2)=.44, χ(2)(12) 145.91, p<.001) demonstrated higher socioeconomic status and less negative attitudes to insulin were associated with increased willingness to initiate insulin.

CONCLUSIONS: Among adults with T2DM for whom insulin is clinically indicated, only one in five are 'very willing' to begin insulin therapy. Independent of demographics, clinical factors and emotional wellbeing, insulin appraisals were associated with 'willingness'. This study highlights the importance of addressing attitudinal barriers to insulin therapy among adults with T2DM in primary care to improve insulin receptiveness.

Measuring the stigma surrounding Type 2 diabetes: development and validation of the Type 2 Diabetes Stigma Assessment Scale (DSAS-2)

OBJECTIVE: To develop and validate a self-report measure of perceived and experienced stigma for use with adults with type 2 diabetes: the Type 2 Diabetes Stigma Assessment Scale (DSAS-2). RESEARCH DESIGN AND METHODS: An item pool was drafted based on qualitative data from 25 adults with type 2 diabetes and content from other health-related stigma questionnaires. Thirteen adults with type 2 diabetes completed 57 draft diabetes stigma items and participated in cognitive debriefing interviews. Based on participant feedback, the pool was reduced to 48 items with a 5-point Likert scale (strongly disagree to strongly agree). A total of 1,064 adults with type 2 diabetes completed a survey including these 48 items and other validated measures. Data were subject to principal components analysis and Spearman ρ correlations. RESULTS: The scale was reduced to 19 items, with an unforced three-factor solution indicative of three subscales: Treated Differently (6 items, α = 0.88), Blame and Judgment (7 items, α = 0.90), and Self-stigma (6 items, α = 0.90). A forced one-factor solution supported the calculation of a total score (α = 0.95). Satisfactory concurrent, convergent, and discriminant validity were demonstrated. CONCLUSIONS: The 19-item DSAS-2 is a reliable and valid measure of type 2 diabetes stigma. A rigorous design and validation process has resulted in a relatively brief measure of perceived and experienced stigma in type 2 diabetes. The novel scale has satisfactory psychometric properties and is now available to facilitate much-needed research in this field.

Moderate-intensity statin therapy seems ineffective in primary cardiovascular prevention in patients with type 2 diabetes complicated by nephropathy:a multicenter prospective 8 years follow up study

Background: Although numerous studies and metanalysis have shown the beneficial effect of statin therapy in CVD secondary prevention, there is still controversy such the use of statins for primary CVD prevention in patients with DM. The purpose of this study was to evaluate the occurrence of total major adverse cardio-vascular events (MACE) in a cohort of patients with type 2 diabetes complicated by nephropathy treated with statins, in order to verify real life effect of statin on CVD primary prevention. Methods: We conducted an observational prospective multicenter study on 564 patients with type 2 diabetic nephropathy free of cardiovascular disease attending 21 national outpatient diabetes clinics and followed them up for 8 years. 169 of them were treated with statins (group A) while 395 were not on statins (group B). Results: Notably, none of the patients was treated with a high-intensity statin therapy according to last ADA position statement. Total MACE occurred in 32 patients from group A and in 68 patients from group B. Fatal MACE occurred in 13 patients from group A and in 30 from group B; nonfatal MACE occurred in 19 patients from group A and in 38 patients from group B. The analysis of the Kaplan-Meier survival curves showed a not statistically significant difference in the incidence of total (p 0.758), fatal (p 0.474) and nonfatal (p 0.812) MACE between the two groups. HbA1c only showed a significant difference in the incidence of MACE between the two groups (HR 1.201, CI 1.041-1.387, p 0.012). Conclusions: These findings suggest that, in a real clinical setting, moderate-intensity statin treatment is ineffective in cardiovascular primary prevention for patients with diabetic nephropathy.

The impact of bariatric surgery on estimated glomerular filtration rate in patients with type 2 diabetes:a retrospective cohort study

Background: Diabetes mellitus is the most common cause of end-stage renal disease, which is associated with increased morbidity and mortality. The impact of bariatric surgery on chronic kidney disease is unclear. Objectives: Our primary aim was to assess the impact of bariatric surgery on estimated glomerular filtration rate (eGFR) in type 2 diabetes (T2D) patients. Our secondary aim was to compare the impact of bariatric surgery versus routine care on eGFR in patients with T2D. Setting: University Hospital, United Kingdom. Methods: A retrospective cohort analysis of adults with T2D who underwent bariatric surgery at a single center between January 2005 and December 2012. Data regarding eGFR were obtained from electronic patients records. eGFR was calculated using the Modification of Diet in Renal Disease formula. Data regarding patients with T2D who did not undergo bariatric surgery ("routine care") were obtained from patients attending the diabetes clinic at the same center from 2009 to 2011. Results: One hundred sixty-three patients were included (mean age 48.5±8.8 yr; baseline body mass index 50.8±9.1 kg/m2) and were followed for 3.0±2.3 years. Bariatric surgery resulted in an improvement in eGFR (median [interquartile range] 86.0 [73.0-100.0] versus 92.0 [77.0-101.0] mL/min/1.73 m2 for baseline versus follow-up, respectively; P = .003), particularly in patients with baseline eGFR≤60 mL/min/1.73 m2 (48.0 [42.0-57.0] versus 61.0 [55.0-63.0] mL/min/1.73 m2; P = .004). After adjusting for baseline eGFR, glycated hemoglobin (HbA1C), body mass index, age, and gender, bariatric surgery was associated with higher study-end eGFR compared with routine care (B = 7.787; P< .001). Conclusion: Bariatric surgery results in significant improvements in eGFR in T2D patients, particularly those with an eGFR≤60 mL/min/1.73 m2, while routine care was associated with a decline in eGFR.

Sustained efficacy of dapagliflozin when added to metformin in type 2 diabetes inadequately controlled by metformin monotherapy

Background and aims: The selective SGLT2 inhibitor dapagliflozin (DAPA) reduces hyperglycaemia independently of insulin secretion or action by inhibiting renal glucose reabsorption. This study (MB102014) is a randomised double-blind, placebo (PBO)-controlled trial of DAPA added to metformin (MET) in T2DM (n=546) inadequately controlled with MET alone. Previously reported short-term data at week 24 showed significant mean reductions in the primary [HbA1c] and secondary [fasting plasma glucose (FPG) and weight] endpoints with DAPA compared to PBO. Here we report efficacy and safety results at week 102 of the long-term extension. Materials and methods: Patients aged 18-77 years with HbA1c 7-10% received DAPA 2.5 mg, 5 mg, 10 mg or PBO, plus open-label MET (≥1500mg/d). Exploratory endpoints at week 102 included changes from baseline in HbA1c, FPG and weight, and were analyzed by longitudinal repeated measures analysis. Results: Overall 71.2% of patients completed 102 weeks of the study; fewer on PBO (63.5%) than on DAPA 2.5 mg, 5 mg, and 10 mg (68.3%, 73.0%, 79.8%), due mainly to more patients on PBO discontinuing for lack of efficacy. At week 102, all DAPA groups showed greater mean reductions from baseline in HbA1c, FPG and weight compared to PBO (table), effects that were similar to those observed at week 24 and maintained throughout the trial. More patients at week 102 also achieved a therapeutic response of HbA1c<7% with DAPA 2.5 mg, 5 mg, and 10 mg (20.7%, 26.4%, 31.5%) than with PBO (15.4%). Adverse events (AEs), serious AEs and AEs leading to discontinuation were balanced across all groups. Signs and symptoms suggestive of genital infection (GenInf) were reported in 11.7%, 14.6%, 12.6% (DAPA 2.5 mg, 5 mg, 10 mg) and 5.1% (PBO) of patients, with 1 discontinuation due to GenInf. Signs and symptoms suggestive of urinary tract infection (UTI) were reported in 8.0%, 8.8%, 13.3% (DAPA 2.5 mg, 5 mg, 10 mg) and 8.0% (PBO), with 1 discontinuation due to UTI. No event of pyelonephritis was reported. Conclusion: In comparison to PBO, DAPA added to MET over 102 weeks demonstrated greater and sustained improvements in glycaemic control, clinically meaningful reduction in weight, and no increased risk of hypoglycaemia in patients with T2DM inadequately controlled with MET alone.

Therapeutic education, the premise of adherence to the type 2 diabetes therapeutic regimen

Background: type 2 diabetes mellitus includes changes in lifestyle in its etiology of prevention, but the evidence is clear —even when people know what to do and what they want to do, they simply do not adopt adherence behaviors. Structured education will allow improving not only metabolic control, but also the adjustment process to a new situation of disease, as well as to develop the patient’s skills in order to make him the key manager of his illness. Objectives: To determine patients’ adherence to prescribed therapeutic regimens. Material and methods: Quantitative, cross-sectional, non-experimental, descriptive, correlational study, with a sample of 102 people with type 2 diabetes, aged between 40 and 85 years old, mostly male (51.96%). The evaluation protocol included social-demographic and clinical questionnaire, Diabetes Self-care Scale and a questionnaire on Diabetes’ knowledge. We also used HbA1c in order to directly assess adherence. Results: It appears that there is no statistically signiicant correlation between socio-demographic variables such as gender and age and adherence. Variables, such as blood glucose monitoring, speciic diet compliance and knowledge, reveal a statistically signiicant effect on adherence (P < .05). Conclusion: The evidence is clear on the urgent need to recognize the importance of measuring patient adherence to a diabetes treatment plan for the maintenance of glycaemic control. We suggest the reinforcement of educational programs in people with type 2 diabetes so as to improve adherence to self-care.

Diabetes Mellitus tipo 1 em Odontopediatria

A Diabetes Mellitus é conhecida por uma doença metabólica caracterizada por um défice na ação ou secreção da insulina, na qual a consequência direta é o aparecimento de hiperglicemia, isto é, o nível de glicose apresentar valores elevados (Kidambi, 2008; Silva-Sousa, 2003). A DM1, especificamente, é apresentada como uma doença que é resultado da destruição das células beta do pâncreas, desenvolvendo assim, um défice na produção de insulina (Raymond et al., 2001). As complicações orais da DM1 incluem xerostomia, doença periodontal (gengivite e periodontite), abcessos dentários, perda de dentes, lesões de tecidos moles e síndrome de ardência oral. A complicação oral mais frequente da DM1 nas crianças é o aumento da sensibilidade à doença periodontal. A doença periodontal é caracterizada como uma reação inflamatória infecciosa dos tecidos gengivais (gengivite) ou do suporte dos dentes, ou seja, ligamento periodontal, cemento e osso alveolar (periodontite), podendo induzir um certo grau de resistência à insulina. Ambas as doenças resultam da interação entre microorganismos periodontais patogénicos. A avaliação e influência do controlo da doença é expressa pelos valores médios de hemoglobina glicosada (Hba1c) na saúde oral nas crianças e adolescentes com DM1. Vários estudos demonstraram que o controlo glicémico teve uma influencia sobre a saúde oral de crianças e adolescentes com DM1. Assim uma avaliação oral, deve fazer parte de procedimentos de rotina no atendimento de crianças e adolescentes com DM1. O dentista deve ser parte da equipa multidisciplinar que auxilia os indivíduos com DM1. O tratamento precoce numa população infantil com DM1, pode diminuir a severidade da doença periodontal. O presente trabalho tem por objectivo realizar uma revisão bibliográfica sobre a importância do estudo em crianças e adolescentes portadores de DM1 e doenças da cavidade oral, nomeadamente, a periodontite, e respetivas implicações.

Anabolic resistance does not explain sarcopenia in patients with type 2 diabetes mellitus, compared with healthy controls, despite reduced mTOR pathway activity

Background Ageing and type 2 diabetes mellitus (T2DM) are risk factors for skeletal muscle loss. We investigated whether anabolic resistance to feeding might underlie accelerated muscle loss in older people with T2DM and whether dysregulated mTOR signalling was implicated. Subjects 8 obese men with T2DM, and 12 age-matched controls were studied (age 68±3 vs. 68±6y; BMI: 30±2 vs. 27±5 kg·m-2). Methods Body composition was measured by dual-X-ray absorptiometry. Insulin and glucose were clamped at post-absorptive concentrations (13±2 vs. 9±3 mU·l-1; 7.4±1.9 vs. 4.6±0.4 mmol·l-1; T2DM vs. controls). Fractional synthetic rates (FSR) of myofibrillar and sarcoplasmic proteins were measured as the rate of incorporation of [13C] leucine during a primed, constant infusion of [1-13C] α-ketoisocaproic acid, 3 h after 10 or 20g of essential amino acids (EAA) were orally administered. Protein expression of total and phosphorylated mTOR signalling proteins was determined by Western blot analysis. Results Despite a significantly lower appendicular lean mass index and a greater fat mass index in T2DM vs. controls, basal myofibrillar and sarcoplasmic and post-prandial myofibrillar FSR were similar. After 20g EAA, stimulation of sarcoplasmic FSR was slightly blunted in T2DM patients. Furthermore, feeding 20g EAA increased phosphorylation of mTOR, p70S6k and 4E-BP1 by 60-100% in controls with no response observed in T2DM. Conclusions There was clear dissociation between changes in mTOR signalling versus changes in protein synthesis rates. However, the intact anabolic response of myofibrillar FSR to feeding in both groups suggests anabolic resistance may not explain accelerated muscle loss in T2DM.

Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss

We investigated the effect of different exercise modalities on high sensitivity-C reactive protein (hs-CRP) and other inflammatory markers in patients with type 2 diabetes and the metabolic syndrome. Eighty-two patients were randomized into 4 groups: sedentary control (A); receiving counseling to perform low-intensity physical activity (B); performing prescribed and supervised high-intensity aerobic (C) or aerobic + resistance (D) exercise (with the same caloric expenditure) for 12 months. Evaluation of leisure-time physical activity and assessment of physical fitness, cardiovascular risk factors and inflammatory biomarkers was performed at baseline and every 3 months. Volume of physical activity increased and HbA1c decreased in Groups B–D. VO2max, HOMA-IR index, HDL-cholesterol, waist circumference and albuminuria improved in Groups C and D, whereas strength and flexibility improved only in Group D. Levels of hs-CRP decreased in all three exercising groups, but the reduction was significant only in Groups C and D, and particularly in Group D. Changes in VO2max and the exercise modalities were strong predictors of hs-CRP reduction, independent of body weight. Leptin, resistin and interleukin-6 decreased, whereas adiponectin increased in Groups C and D. Interleukin-1β, tumor necrosis factor-α and interferon-γ decreased, whereas anti-inflammatory interleukin-4 and 10 increased only in Group D. In conclusion, physical exercise in type 2 diabetic patients with the metabolic syndrome is associated with a significant reduction of hs-CRP and other inflammatory and insulin resistance biomarkers, independent of weight loss. Long-term high-intensity (preferably mixed) training, in addition to daytime physical activity, is required to obtain a significant anti-inflammatory effect.

Determination of metabolic equivalents during low-and high-intensity resistance exercise in healthy young subjects and patients with type 2 diabetes

The purpose of this study was to quantify the metabolic equivalents (METs) of resistance exercise in obese patients with type 2 diabetes (T2DM) and healthy young subjects and to evaluate whether there were differences between sessions executed at low- versus high-intensity resistance exercise. Twenty obese patients with T2DM (62.9±6.1 years) and 22 young subjects (22.6±1.9 years) performed two training sessions: one at vigorous intensity (80% of 1-repetition maximum (1RM)) and one at moderate intensity (60% of 1RM). Both groups carried out three strength exercises with a 2-day recovery between sessions. Oxygen consumption was continuously measured 15 min before, during and after each training session. Obese T2DM patients showed lower METs values compared with young healthy participants at the baseline phase (F= 2043.86; P<0.01), during training (F=1140.59; P<0.01) and in the post-exercise phase (F=1012.71; P<0.01). No effects were detected in the group x intensity analysis of covariance. In this study, at both light-moderate and vigorous resistance exercise intensities, the METs value that best represented both sessions was 3 METs for the obese elderly T2DM patients and 5 METs for young subjects.