Basal insulin treatment intensification in patients with type 2 diabetes mellitus: A comprehensive systematic review of current options

AimAs type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium–glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin.MethodsMEDLINE, EMBASE and EBSCOhost were searched for English-language articles, and all those captured were original articles (case studies and narrative reviews were omitted). Data on study design, population demographics, interventions and outcomes were tabulated. The extracted outcome data included changes in glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), as well as body weight and safety data.ResultsA total of 88 publications were deemed relevant. All treatments reduced HbA_1c and FPG. The most pronounced reductions in PPG, an unmet need in patients not controlled by basal insulin, were seen following administration of RAIs and short-acting GLP-1 RAs, although data for this outcome are generally lacking. Body weight benefits were observed with GLP-1 RAs and SGLT-2 inhibitors. However, as only articles in English were included, the result was a possible publication bias, while the diversity of study designs and drug combinations limited comparisons between studies.ConclusionThe evidence supports effectiveness of the available add-on treatments to basal insulin. However, other factors, such as potential body-weight increases, convenience/compliance and adverse events, particularly hypoglycaemia, should be considered on a patient-by-patient basis to optimalize treatment outcomes.     

Impaired endothelial function is not associated with arterial stiffness in adults with type 1 diabetes

AimThis study investigated the relationship between endothelial dysfunction (ED) and arterial stiffness (AS) in adults with type 1 diabetes and no clinical cardiovascular (CV) disease.MethodsA total of 68 patients with type 1 diabetes and 68 age- and gender-matched healthy (non-diabetic) subjects were evaluated. ED was assessed by reactive hyperaemia peripheral arterial tonometry (RH-PAT) and by serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin. AS was assessed by aortic pulse wave velocity (aPWV). All statistical analyses were stratified by gender.ResultsAdults with type 1 diabetes had RH-PAT index scores similar to those of their matching controls [men: 1.55 (1.38–1.98)% versus 1.61 (1.40–2.17)%, P = 0.556; women: 2.07 (1.55–2.31)% versus 2.08 (1.79–2.49)%; P = 0.215]. However, after adjusting for potential confounders, type 1 diabetes emerged as the main determinant of the RH-PAT index in women. Also, differences between genders in both the controls and type 1 diabetes patients disappeared. Men with diabetes had higher serum concentrations of E-selectin, and women had higher serum concentrations of sICAM-1, sVCAM-1 and E-selectin than their respective controls. However, after adjusting for potential confounders, only the differences in sICAM-1 (women) and E-selectin (both genders) remained significant. No association was found between aPWV and the RH-PAT index and ED markers after adjusting for CV risk factors.ConclusionED was increased in adults with type 1 diabetes compared with age-matched non-diabetic subjects. Also, gender differences in ED were lost in type 1 diabetes. However, ED was not associated with AS after adjusting for potential confounders. These findings suggest that ED occurs earlier than AS in type 1 diabetes.     

Microalbuminuria,but not reduced eGFR,is associated with cardiovascular subclinical organ damage in type 2 diabetes

AimThis study explored the association between reduced estimated glomerular filtration rate (eGFR) and microalbuminuria vs. subclinical organ damage in patients with type 2 diabetes.MethodsData from middle-aged patients with type 2 diabetes (n = 706) treated in primary care were analyzed for microalbuminura, defined as a urinary albumin/creatinine ratio (uACR) ≥ 3.0 mmol/mol, and reduced eGFR, defined as < 60 mL/min/1.73 m², in relation to blood pressure, pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima–media thickness (IMT) and lumen diameter (LD).ResultsPatients with microalbuminuria had significantly higher 24-h ambulatory systolic blood pressure (ASBP) compared with subjects with uACR < 3 mg/mmol: 137 vs. 128 mmHg (P < 0.001). There were no differences in ASBP in patients with eGFR < 60 mL/min/1.73 m². However, patients with vs. without microalbuminuria had increased PWV (11.4 vs. 10.1 m/s; P < 0.001), LVMI (134.4 vs. 118.6 g/m²; P < 0.001), LD (7.01 ± 0.93 vs. 6.46 ± 0.74 mm; P < 0.001) and IMT (0.78 vs. 0.74 mm; P = 0.047), respectively. The associations between uACR vs. PWV and LVMI were more robust after adjusting for age, diabetes duration, ASBP, HbA_1c, LDL-cholesterol, and antihypertensive and lipid-lowering therapy compared with uACR vs. IMT. There were no statistically significant differences in PWV, LVMI or IMT between patients with reduced (< 60 mL/min/1.73 m²) vs. normal eGFR.ConclusionLevels of urinary albumin excretion, but not reduced eGFR, were associated with increased arterial stiffness, left ventricular mass and atherosclerosis in patients with type 2 diabetes.     

Sex hormone levels are not associated with progression of renal disease in male patients with T2DM

BackgroundGreater renal function decline (RFD) in type 2 diabetes (T2DM) has been suggested in men compared with women, and imbalances in estrogen/androgen levels have been associated with cardiovascular disease mortality in elderly men, but it remains unclear whether sex hormone disequilibrium is related to diabetic nephropathy (DN) in men with T2DM.ObjectiveThis study examined the relationship between sex steroid concentrations and renal outcomes in male T2DM patients.Population and methodsTotal testosterone (T), total estradiol (E2), sex hormone-binding globulin (SHBG), and total and calculated free (cf) E2/T ratios were compared in 735 male T2DM patients with (n = 513) and without (n = 222) DN, using a cross-sectional approach. Also, in a pilot complementary prospective nested case-control cohort, total E2/total T and cfE2/cfT were evaluated according to a hard renal outcome (HRO): end-stage renal disease/doubling of baseline serum creatinine (36 HRO cases, 72 HRO controls) and rate of eGFR decline (68 rapid vs 68 slow RFD).ResultWith the cross-sectional approach, E2 and cfE2 were higher in DN cases vs DN controls (95.5 vs 86.8 pmol/L [P = 0.0246] and 2.59 vs 2.36 pmol/L [P = 0.005], respectively). The difference in E2 persisted on multivariate analysis. In the prospective approach, E2 and T concentrations, and total E2/total T and cfE2/cfT2 ratios did not differ in HRO cases vs controls or in patients with rapid vs slow RFD.ConclusionAlthough positively related to DN in the cross-sectional analysis, progression of renal disease in male patients with T2DM was not related to either sex hormone levels or aromatase index as reflected by E2/T ratio.     

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension)

AimsTo compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months.MethodsEDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed.ResultsThe 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA_1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00–05:59 h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24 h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments.ConclusionOver 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results.     

T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population

AimAdiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population.MethodsTwo polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n = 5212) and people with T2D in the DIABHYCAR study (n = 3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n = 230), and in controls who remained normoglycaemic (n = 226) throughout.ResultsIn a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04–1.18; P = 0.001) and 0.92 (95% CI: 0.87–0.98; P = 0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P = 0.03) and HbA_1c (P = 0.006), and lower plasma adiponectin levels (P = 0.03) in the D.E.S.I.R. participants. Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P = 0.03), HbA_1c (P = 0.02) and Fatty Liver Index (FLI; P ≤ 0.01), and higher plasma adiponectin levels (P = 0.002). Associations with HbA_1c, FLI and adiponectin levels persisted after adjusting for BMI.ConclusionCDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.     

Relationship between olfactory dysfunction and cognitive impairment in elderly patients with type 2 diabetes mellitus

AimsRecent clinical studies identified the relation between olfactory dysfunction and cognitive impairment in the elderly without type 2 diabetes mellitus. The aim of the present study was to define the relation between olfactory function and cognition in elderly patients with type 2 diabetes mellitus.MethodsThe study participants comprised 250 elderly (age, 68–77, median 72) Japanese outpatient with type 2 diabetes mellitus free of clinically-evident cognitive impairment. Olfactory and cognitive functions were evaluated by the Open Essence (OE) test and Mini-mental State Examination (MMSE), respectively.ResultsBased on the MMSE score, 62.0%, 24.4%, and 13.6% of the participants were considered to have no impairment, possible cognitive impairment and probable dementia, respectively. The OE test score of the probable dementia group was significantly lower than other groups. Furthermore, age and serum uric acid were significantly higher in the probable dementia group than other groups. Simple correlation analysis showed positive correlation between the MMSE score and diastolic blood pressure, education, OE test score, total cholesterol, LDL cholesterol, folic acid, and negative correlation with age, HbA_1c, aspartate aminotransferase, serum adiponectin and urinary albumin excretion. Multivariate regression analysis showed that OE test score correlated significantly and independently with MMSE score (standardized coefficients β = 0.542, R² = 0.478, P < 0.01), in addition to education level, HbA1c and serum adiponectin.ConclusionsThe results suggested the association of olfactory dysfunction with cognitive impairment in elderly patients with type 2 diabetes mellitus.     

Usefulness of the plasma glucose concentration-to-HbA1c ratio in predicting clinical outcomes during acute illness with extreme hyperglycaemia

AimsTo evaluate the correlation between the plasma glucose-to-glycated haemoglobin ratio (GAR) and clinical outcome during acute illness.MethodsThis retrospective observational cohort study enrolled 661 patients who visited the emergency department of our hospital between 1 July 2008 and 30 September 2010 with plasma glucose concentrations > 500 mg/dL. Systolic blood pressure, heart rate, white blood cells, neutrophils, haematocrit, blood urea nitrogen, serum creatinine, liver function and plasma glucose concentration were recorded at the initial presentation to the emergency department. Data on glycated haemoglobin over the preceding 6 months were reviewed from our hospital database. The glucose-to-HbA_1c ratio (GAR) was calculated as the plasma glucose concentration divided by glycated haemoglobin.ResultsThe GAR of those who died was significantly higher than that of the survivors (81.0 ± 25.9 vs 67.6 ± 25.0; P < 0.001). There was a trend towards a higher 90-day mortality rate in patients with higher GARs (log-rank test P < 0.0001 for trend). On multivariate Cox regression analysis, the GAR was significantly related to 90-day mortality (hazard ratio [HR] for 1 standard deviation [SD] change: 1.41, 95% confidence interval [CI]: 1.22–1.63; P < 0.001), but not to plasma glucose (HR: 0.89, 95% CI: 0.70–1.13; P = 0.328). Rates of intensive care unit (ICU) admission and mechanical ventilator use were also higher in those with higher GARs.ConclusionGAR independently predicted 90-day mortality, ICU admission and use of mechanical ventilation. It was also a better predictor of patient outcomes than plasma glucose alone in patients with extremely high glucose levels.     

Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials

BackgroundGuidelines for type 2 diabetes (T2D) recommend reducing HbA_1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial.MethodsA systematic review of the literature (PubMed, Cochrane Library Central Register of Controlled Trials [CENTRAL] and https://clinicaltrials.gov), including all RCTs vs placebo published up to May 2015 and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), published June 2015, was performed. Primary endpoints were all-cause mortality and death from cardiovascular causes; secondary endpoints were macrovascular and microvascular events. Safety endpoints were acute pancreatitis, pancreatic cancer, serious adverse events and severe hypoglycaemia.ResultsA total of 36 double-blind RCTs were included, allowing analyses of 54,664 patients. There were no significant differences in all-cause mortality (RR = 1.03, 95% confidence interval [CI] = 0.95–1.12), cardiovascular mortality (RR = 1.02, 95% CI = 0.92–1.12), myocardial infarction (RR = 0.98, 95% CI = 0.89–1.08), strokes (RR = 1.02, 95% CI = 0.88–1.17), renal failure (RR = 1.06, 95% CI = 0.88–1.27), severe hypoglycaemia (RR = 1.14, 95% CI = 0.95–1.36) and pancreatic cancer (RR = 0.54, 95% CI = 0.28–1.04) with the use of DPP-4Is. However, DDP-4Is were associated with an increased risk of heart failure (RR = 1.13, 95% CI = 1.01–1.26) and of acute pancreatitis (RR = 1.57, 95% CI = 1.03–2.39).ConclusionThere is no significant evidence of short-term efficacy of DPP-4Is on either morbidity/mortality or macro-/microvascular complications in T2D. However, there are warning signs concerning heart failure and acute pancreatitis. This suggests a great need for additional relevant studies in future.     

Impact of flexible insulin therapy on blood glucose variability,oxidative stress and inflammation in type 1 diabetic patients: The VARIAFIT study

AimsHbA_1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress.MethodsTests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E₄ (LTE4), 11-dehydro-thromboxane B₂ (TXB2) and 8-iso-prostaglandin F2α (PGF2).ResultsHbA_1c (7.7 ± 0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832 ± 625 vs. 633 ± 972 pg/mg; P = 0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r ≥ 0.84, P < 0.0001).ConclusionA FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA_1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation (ClinicalTrials.gov NCT00973492).     

Obstructive sleep apnea and type 2 diabetes: interacting epidemics

Type 2 diabetes is a major public health concern with high morbidity, mortality, and health-care costs. Recent reports have indicated that the majority of patients with type 2 diabetes also have obstructive sleep apnea (OSA). There is compelling evidence that OSA is a significant risk factor for cardiovascular disease and mortality. Rapidly accumulating data from both epidemiologic and clinical studies suggest that OSA is also independently associated with alterations in glucose metabolism and places patients at an increased risk of the development of type 2 diabetes. Experimental studies in humans and animals have demonstrated that intermittent hypoxia and reduced sleep duration due to sleep fragmentation, as occur in OSA, exert adverse effects on glucose metabolism. Based on the current evidence, clinicians need to address the risk of OSA in patients with type 2 diabetes and, conversely, evaluate the presence of type 2 diabetes in patients with OSA. Clearly, there is a need for further research, using well-designed studies and long-term follow-up, to fully demonstrate a causal role for OSA in the development and severity of type 2 diabetes. In particular, future studies must carefully consider the confounding effects of central obesity in examining the link between OSA and alterations in glucose metabolism. The interactions among the rising epidemics of obesity, OSA, and type 2 diabetes are likely to be complex and involve multiple pathways. A better understanding of the relationship between OSA and type 2 diabetes may have important public health implications.     

Electrocardiographic changes associated with insulin resistance

Background and aimCardiac steatosis has been related to increased risk of heart disease. We investigated the association between cardiac steatosis, electrocardiographic (ECG) abnormalities, and individual components of the metabolic syndrome (MetS).Methods and resultsA 12-lead ECG and laboratory data were examined in 31 men with the MetS and in 38 men without the MetS. Myocardial triglyceride (MTG) content was measured with 1.5 T magnetic resonance (MR) spectroscopy and epicardial and pericardial fat by MR imaging. MTG content, epicardial and pericardial fat depots were higher in men with the MetS compared with subjects without the MetS (p < 0.001). The heart rate was increased (p < 0.001), the PR interval was longer (p < 0.044), the frontal plane QRS axis shifted to the left (p < 0.001), and the QRS voltage (p < 0.001) was lower in subjects with the MetS. The frontal plane QRS axis and the QRS voltage were inversely correlated with MTG content, waist circumference (WC), body mass index (BMI), TGs, and fasting blood glucose. High-density lipoprotein cholesterol correlated positively and measures of insulin resistance negatively with the QRS voltage. MTG content and hypertriglyceridemia were determinants of the frontal plane QRS and WC and hyperglycemia were predictors of the QRS voltage.ConclusionThe MetS and cardiac steatosis appear to associate with multiple changes on 12-lead ECG. The frontal plane QRS axis is shifted to the left and the QRS voltage is lower in subjects with the MetS. Standard ECG criteria may underestimate the presence of left ventricular hypertrophy in obese subjects with cardiometabolic risk factors.     

Prevalence of exocrine pancreatic insufficiency in type 2 diabetes mellitus with poor glycemic control

ObjectivesTo evaluate the relationship between exocrine pancreatic insufficiency and the level of glycemic control in diabetes (DM).MethodsPatients with type 2 DM treated in our clinic were prospectively recruited into the study. Pancreatic diabetes was excluded. Cases with HbA1c ≥7% formed Group A (n = 59), and with HbA1c <7% Group B (n = 42). The fecal level of pancreatic elastase (PE-1) was measured and morphological examinations of the pancreas were performed.ResultsThe PE-1 level was significantly lower in Group A than in Group B (385.9 ± 171.1 μg/g, vs. 454.6 ± 147.3 μg/g, p = 0.038). The PE-1 level was not correlated with HbA1c (r = −0.132, p = 0.187), the duration of DM (r = −0.046, p = 0.65), age (r = 0.010, p = 0.921), BMI (r = 0.203, p = 0.059), or pancreatic steatosis (r = 0.117, p = 0.244). The size of the pancreas did not differ significantly between Groups A and B.ConclusionsAn exocrine pancreatic insufficiency demonstrated by fecal PE-1 determination is more frequent in type 2 DM patients with poor glycemic control. The impaired exocrine pancreatic function cannot be explained by an alteration in the size of the pancreas or by pancreatic steatosis.     

Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus

As skin autofluorescence (AF) can assess subcutaneous accumulation of fluorescent advanced glycation end-products (AGEs), this study aimed to investigate whether it was linked to glycaemic control and complications in patients with type 1 diabetes mellitus (T1DM). Using the AGE Reader™, AF was measured in T1DM patients referred to Haut-Levêque Hospital (Bordeaux, France); data on their HbA_1c levels measured every 6 months as far back as the last 5 years were also collected. The association of AF with the patients’ past glucose control, based on their latest HbA_1c values, and the means of the last five and 10 HbA_1c values, and with diabetic complications was also examined by linear regression analysis. The sample included 300 patients: 58% were male; the mean age was 49 (SD 17) years and the mean diabetes duration was 21 (SD 13) years. The median skin AF measurement was 2.0 [25th–75th percentiles: 1.7–2.4] arbitrary units (AU), and this was associated with age (β = 0.15 per 10 years, P < 0.001) and diabetes duration (β = 0.17 per 10 years, P < 0.001). After adjusting for age and estimated glomerular filtration rate (eGFR), the skin AF measurement was also related to the means of the last five and 10 HbA_1c values (β = 0.10 per 1% of HbA_1c, P = 0.005, and β = 0.13 per 1% of HbA_1c, P = 0.001, respectively). In addition, the skin AF was associated with retinopathy (P < 0.001), albuminuria (P < 0.001) and decreased eGFR (P < 0.001). In conclusion, the skin AF is related to the long-term glucose control and diabetic complications.     

Adiponectin is expressed in the pancreas of high-fat-diet-fed mice and protects pancreatic endothelial function during the development of type 2 diabetes

AimAdiponectin levels in skeletal muscle and adipose tissue have been reported to be involved in insulin resistance in rats fed with a high-fat diet (HFD). Our objective was to explore whether adiponectin is also expressed in the pancreas and what its potential role is during the development of type 2 diabetes (T2D) in outbred CD-1 mice.MethodsMale 4-week-old outbred CD-1 mice were fed an HFD to induce a polygenic model of human T2D. Adiponectin expression was examined in mouse pancreas by quantitative real-time polymerase chain reaction (qPCR), western blots and immunofluorescence analyses. Human umbilical vein endothelium cells (HUVECs) were transfected with an adiponectin-expressing lentivirus to determine the effect of adiponectin on angiogenic function in vitro.ResultsFeeding mice an HFD for 9 weeks resulted in constant hyperglycaemia, obesity, impaired glucose tolerance and insulin resistance. Additional hyperinsulinaemia emerged in mice fed an HFD for 18 weeks. Interestingly, aberrant expression of adiponectin was detectable in the pancreatic vascular endothelial cells (VECs) of mice fed with an HFD, but not in mice fed with regular chow (RC). Expression levels of pancreatic adiponectin varied during the development of T2D. This extraordinary expression of adiponectin in pancreatic VECs played a role in protecting endothelial function against potential damage by HFD. Our in vitro study has demonstrated that adiponectin promotes angiogenic function.ConclusionThese results reveal for the first time that adiponectin is expressed in pancreatic VECs of HFD-fed mice during the development of T2D as a protective adaptation in response to the HFD.     

Persistent airway obstruction after virus infection is not associated with airway inflammation

BACKGROUND: This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. METHODS: Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. RESULTS: Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1 percent predicted [Delta%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Delta%FEV1, > or = 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. CONCLUSION: Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.     

Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)

BackgroundA family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives.MethodsData from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age < 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes.ResultsBoth FHD–T1D (OR: 5.8; 95% CI: 3.2–10.3) and FHD–T2D (OR: 1.9; 95% CI: 1.5–2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD–T2D (OR: 2.7; 95% CI: 2.2–3.3), but not FHD–T1D. In LADA patients, FHD–T1D vs FHD–T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576).ConclusionThe risk of LADA is substantially increased with FHD–T1D but also, albeit significantly less so, with FHD–T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD–T1D had more T1D-like features, emphasizing the heterogeneity of LADA.