Impaired diffusing capacity for carbon monoxide in children with type 1 diabetes: is this the first sign of long-term complications?

We assessed the presence of lung dysfunction in children with type 1 diabetes, evaluated as reduced diffusing capacity of the lung for carbon monoxide (DLCO), and its components: membrane diffusing capacity (DM) and pulmonary capillary blood volume (Vc). A total of 42 children, aged 15.6 ± 3.8 years, with type 1 diabetes for 8.3 ± 5.5 years, and 30 healthy age and sex-matched peers were recruited for the study. Lung volumes and spirometric dynamic parameters were assessed by plethysmography. Single-breath DLCO was measured according to international recommendation. DM and Vc volume were calculated. Lung volumes were significantly reduced in young patients with type 1 diabetes when compared to controls. Moreover, DLCO was reduced in patients compared to controls (78% ± 16% vs. 120% ± 1%, P = 0.0001). However, when differentiating DM and Vc compartments, we observed a significant impairment only about Vc (34 ± 20 ml vs. 88 ± 18 ml; P = 0.0001), while no difference was observed about DM compartment (23 ± 4 vs. 26 ± 3 ml/min/mmHg, P = 0.798). Whether this might be seen as the “first” sign of microangiopathic involvement in patients with type 1 diabetes has to be confirmed on larger groups but is still fascinating. Meanwhile, we suggest to screen DLCO in all patients with type 1 diabetes.     

Specific phenotype associated with diabetes mellitus secondary to chronic hepatitis C infection

Aim A link between chronic hepatitis C virus (HCV) infection, Type 2 diabetes mellitus and insulin resistance has been suggested by several studies. However, HCV infection appears to be associated with insulin resistance but not with the metabolic syndrome. The aim of this study was to determine whether chronic HCV infection had an impact on the clinical characteristics of Type 2 diabetes. Methods We studied retrospectively a group of patients with diabetes mellitus associated with HCV infection (HCV‐DM) and compared them with patients with conventional Type 2 diabetes (DM). Results The HCV‐DM patients had a lower body mass index (P = 0.001) and systolic blood pressure (P = 0.04) compared with patients with DM diabetes. Ten patients (27.0%) in the HCV‐DM group and 35 (47.3%) in the DM group had microalbuminuria (P = 0.04). DM patients had significantly higher serum creatinine levels than HCV‐DM patients [87 (72–108) vs. 77 (64–86) µmol/l, P = 0.02; median (interquartile range)] but creatinine clearance (Cockroft Gault calculation) was similar. One HCV‐DM patient (2.7%) and 44 DM patients (59.4%) were treated with hypolipidaemic therapy (P = 0.0001). Even although nearly two‐thirds of the overall DM group were prescribed cholesterol‐lowering drugs, DM patients had significantly higher total cholesterol, high‐density lipoprotein cholesterol and triglyceride levels than HCV‐DM patients. Conclusion Our study provides further evidence that HCV‐DM patients have specific clinical characteristics in comparison with classical DM patients. These data suggest an association between HCV virus infection and the development of insulin resistance or diabetes mellitus without the typical features of the metabolic syndrome.     

Hepatitis C virus eradication with direct‐acting antiviral improves insulin resistance

Sustained virological response (SVR) after interferon‐based therapy is associated with improvement of insulin resistance (IR) in HCV‐infected patients. Few data are available in the direct‐acting antivirals (DAAs) era, especially in cirrhotic patients. We prospectively evaluated the long‐term effect of DAAs on IR. Patients treated with DAAs between May 2015 and December 2016 in 3 tertiary care centres were recruited. Patients with diabetes were excluded. Biochemical and virological data were collected at baseline, 12/24/48 weeks (W) after the end of therapy (EOT). Presence of IR was defined by a ‘homeostasis model assessment index for IR’ [HOMA‐IR])> 2.5. Liver fibroscan was performed at baseline, at 24/48W after EOT. Hundred and thirty‐eight patients were enrolled (mean age 58 years, M/F 85/53, GT1 61%, 68.8% cirrhotic). Sixty‐eight patients (94/138) had IR. Patients with IR had significantly higher stiffness than patients without it (23 ± 12 vs 15 ± 8; P < .0001). SVR12 was achieved in 135 (98%) patients, and 124 (90%) patients reached the 48W post‐EOT. At this time point, the percentage of patients with IR significantly decreased to 49% (P = 0,01). HOMA‐IR was significantly lower than baseline (1.8 vs 3; P < .001), and this was related to a significant reduction of insulin level (11.7 ± 6.3 vs 16.4 ± 8.3). High BMI was associated with a significantly lower probability of achieving a non‐IR status at 24W (P = .05) and 48W (P = .03).In conclusion, SVR following DAAs led to a significant reduction of IR, even in patients with cirrhosis. Nevertheless, IR can persist after the achievement of SVR, especially in patients with high BMI.     

Impact of non‐alcoholic fatty liver disease on microalbuminuria in patients with prediabetes and diabetes

Background: It is unknown whether microalbuminuria is associated with non‐alcoholic fatty liver disease (NAFLD) among patients with prediabetes and type 2 diabetes mellitus (DM). This study investigated the association of NAFLD with microalbuminuria among patients with prediabetes and diabetes. Methods: We evaluated 1361 subjects who had an abnormal oral glucose tolerance test (OGTT) on routine screening. All participants were divided into two groups, prediabetes and newly diagnosed type 2 DM, and the association of NAFLD with metabolic parameters on microalbuminuria was analysed. Results: The patients with NAFLD had higher prevalence rates of microalbuminuria (6.3% vs 19%; P= 0.001 in prediabetes, 4.5% vs 32.6%; P < 0.001 in diabetes) and also had a greater albumin‐to‐creatinine ratio (14.6 ± 52.0 µg/mg Cr vs 27.7 ± 63.9 µg/mg Cr; P= 0.051 in prediabetes, 11.4 ± 21.4 µg/mg Cr vs 44.7 ± 76.4 µg/mg Cr; P < 0.001 in diabetes) than those without NAFLD. The logistic regression analysis showed that NAFLD was associated with increased rates of microalbuminuria (odds ratio 3.66; 95% confidence interval (CI) 1.31–10.20, P= 0.013 in prediabetes, odds ratio 5.47; 95% CI 1.01–29.61, P= 0.048 in diabetes), independently of age, sex, body mass index, waist circumference, liver enzymes, lipid profiles, HbA1c, insulin resistance as estimated by homeostasis model assessment, hypertension, smoking status and the metabolic syndrome. Conclusions: The results of our study revealed a strong relationship between microalbuminuria and NAFLD in the patients with prediabetes and newly diagnosed diabetes. Further studies are required to confirm whether NAFLD is a predictor of the development of microalbuminuria in patients with prediabetes and diabetes.     

Correlation between markers of peripheral nerve function and structure in type 1 diabetes

Background

Clinical and experimental studies in patients with type 1 and type 2 diabetes have demonstrated changes in ion channel function and nerve structure. In this study, we investigated the relationship between axonal dysfunction and morphological change in diabetic polyneuropathy by using neuromuscular ultrasound and nerve excitability techniques. We also explored possible differences in this relationship between type 1 and type 2 diabetes.

Methods

Nerve ultrasound and corresponding motor excitability studies were undertaken in 110 diabetes patients (50 type 1; 60 type 2) and 60 age‐matched controls (30 for each group). Neuropathy severity was assessed by using total neuropathy score. Median and tibial nerve cross‐sectional areas were measured at nonentrapment sites by using high‐resolution linear probe.

Results

Median and tibial nerve cross‐sectional areas were significantly higher in diabetes patients compared with controls: type 1 (median = 7.6 ± 0.2 mm² vs 6.3 ± 0.1 mm²; tibial = 14.5 ± 0.7 mm² vs 10.8 ± 0.3 mm², P < .05) and type 2 (median = 9.1 ± 0.3 mm² vs 7.2 ± 0.1 mm²; tibial = 18.5 ± 1.0 mm² vs 12.8 ± 0.5 mm², P < .05). In the type 1 cohort, significant correlations were found between nerve cross‐sectional area and excitability parameters including resting current‐threshold slope (median: r = 0.523, P < .0001; tibial: r = ?0.571, P = .004) and depolarizing threshold electrotonus at 90 to 100 ms (median: 0.424, P < .01; tibial: r = 0.435, P = .030). In contrast, there was no relationship between excitability values and nerve cross‐sectional area in the type 2 cohort.

Conclusions

This study has identified correlation between markers of axonal membrane function and structural abnormalities in peripheral nerves of type 1 diabetes patients. The differential relationship in nerve function and structure between type 1 and type 2 diabetes provides clinical evidence that different pathophysiological mechanisms underlie the development of neuropathy in these patient groups.     

Insulin resistance is an independent correlate of increased urine albumin excretion: a cross‐sectional study in Iranian Type 2 diabetic patients

Aims To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. Methods Three hundred and sixty‐one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005–2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE ≥ 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA‐IR). Results HOMA‐IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA‐IR were 11.81 ± 7.51 (mg/day) and 3.30 ± 2.21 in normoalbuminuric and 75.36 ± 55.57 (mg/day) and 4.98 ± 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA‐IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA‐IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7–6.2)]. Conclusions In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA‐IR is an independent predictor of UAE.     

Age‐related difference of the association of cardiovascular risk factors with the cardio‐ankle vascular index in the Cardiovascular Prognostic Coupling Study in Japan (the Coupling Registry)

The value of the cardio‐ankle vascular index (CAVI) increases with age. All large‐scale studies of the CAVI have investigated patients <80 years old. Thus, the clinical characteristics of high CAVI in patients aged 80 or more remain unclear. Therefore, we investigated (1) the CAVI in very elderly patients and (2) the determinants of a high CAVI in high‐risk patients, including very elderly patients. The Cardiovascular Prognostic Coupling Study in Japan (Coupling Registry) is a prospective observational study of Japanese outpatients with any cardiovascular risk factors. We enrolled 5109 patients from 30 institutions (average age 68.7 ± 11.4 years, 52.4% males). We investigated the determinants of the CAVI by separating the patients into three groups: 970 middle‐aged (<60 years), 3252 elderly (60‐79 years), and 887 very elderly (≥80 years) patients. The CAVI values of the males were significantly higher those of the females in all age groups (<60 years: 7.81 ± 1.11 vs. 7.38 ± 0.99, P < .001; 60‐79 years: 9.20 ± 1.29 vs. 8.66 ± 1.07, P < .001; ≥80 years: 10.26 ± 1.39 vs. 9.51 ± 1.12, P < .001). In all age groups, the CAVI of the patients with diabetes/glucose tolerance disorder was higher than that of the patients without diabetes/glucose tolerance disorder (<60 years: 7.82 ± 1.22 vs 7.58 ± 1.03, P = .002; 60‐79 years: 9.23 ± 1.20 vs 8.78 ± 1.19, P < .001; ≥80 years: 10.04 ± 1.24 vs 9.75 ± 1.32, P = .002). The determinants of the CAVI in these very elderly patients were age, male sex, low BMI, and mean blood pressure. Diabetes/glucose tolerance disorder and glucose were independently associated with the CAVI in the patients aged <60 years and 60‐79 years, but not in those aged ≥80 years after adjusting for other covariates.     

Comparison of day‐to‐day blood pressure variability in hypertensive patients with type 2 diabetes mellitus to those without diabetes: Asia BP@Home Study

Blood pressure variability (BPV) has been shown to be independently associated with cardiovascular (CV) mortality and morbidity. Patients with type 2 diabetes mellitus (T2DM) have also been shown to have increased BPV. We aimed to compare BPV in hypertensive patients with diabetes with those without diabetes. A total of 1443 hypertensive patients measured their blood pressure (BP) twice in the morning and twice before bed at home for a week. Demographic data, history of T2DM, and anti‐hypertensive use were captured. Clinic BP was measured twice in the clinic. Control of BP was defined as clinic systolic BP (SBP) <140 mm Hg and home SBP < 135 mm Hg. BPV was based on home SBP measurements. A total of 362(25.1%) hypertensives had diabetes and 47.4% were male. Mean age was 62.3 ± 12.1 years. There was no difference in the mean clinic SBP in both groups (139.9 mm Hg vs 138.4 mm Hg P = .188). However, the mean morning home SBP was significantly higher and control rate lower in hypertensives with diabetes than those without (132.3 ± 15 mm Hg vs 129.7 ± 14.4 mm Hg P = .005, 39.4% vs 47.6% P = .007), respectively. Masked uncontrolled morning hypertension was higher in those with diabetes versus those without (12.8% vs 8.4%, respectively). There was no statistically significant difference in BPV between those with and without diabetes. In summary, clinic SBP was similar in hypertensives with or without diabetes. However, control of BP based on both clinic and home SBP thresholds was poorer in hypertensives with diabetes compared to those without. Masked uncontrolled morning hypertension was higher in those with diabetes than those without. There was no difference in BPV between the two groups.     

High‐normal levels of albuminuria predict the development of micro‐ and macroalbuminuria and increased mortality in Brazilian Type 2 diabetic patients: an 8‐year follow‐up study

Aim To analyse the risk factors for the development of micro‐ and macroalbuminuria and mortality rates in a cohort of normoalbuminuric Type 2 diabetes mellitus (DM) patients. Methods In this prospective study, 193 Type 2 DM patients with urinary albumin excretion (UAE) < 20 µg/min, 96 men (50%), aged 56.5 ± 9 years, were followed for a mean period of 8 ± 3 years. UAE and estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) were measured. The outcomes were development of persistent micro‐ and macroalbuminuria and mortality. Results Twenty patients were lost to follow‐up. Of the 173 remaining patients, 33 (19%) died. The Cox analysis [hazard ratio (HR), 95% confidence interval] revealed that the baseline significant predictors of mortality were higher UAE [above median (5 µg/min); HR 2.7, 1.2–6.1; P = 0.02], male sex (HR  3.9, 1.7–9.2; P = 0.002), age (HR 1.6, 1.3–1.9; P = 0.0001), and fasting plasma glucose (HR 1.2, 1.1–1.3; P = 0.004). Smoking and eGFR were not significant in this model. Follow‐up renal data were available for 158 patients: 34 (22%) progressed to microalbuminuria and seven (4%) to macroalbuminuria, and the baseline predictors were a higher UAE (> 5 µg/min, HR 2.5, 1.2–5.1; P = 0.02), presence of diabetic retinopathy (HR 2.5, 1.3–5.0; P = 0.009), fasting glucose (HR 1.1, 1.0–1.2; P = 0.015), and male sex (HR 2.2, 1.1–4.7; P = 0.04), independently of smoking and hypertension. Lower GFR (HR 0.98, 0.97–1.00; P = 0.07) was of borderline significance. Conclusions In normoalbuminuric Type 2 DM patients, the development of micro‐ or macroalbuminuria and mortality rates was independently and positively associated with higher levels of albuminuria, although still in the traditionally established normal range.     

Safety and efficacy of catheter ablation of atrial fibrillation in patients with diabetes mellitus—single center experience

Background and objective Little is known about the outcome of catheter ablation of atrial fibrillation (AF) in patients with diabetes mellitus (DM). We investigated the safety and efficacy of catheter ablation of AF in patients with DM. Materials and methods Thirty one patients with DM from a group of 263 consecutive patients undergoing a first-time catheter ablation of AF procedure were enrolled in a prospective study. The ablation protocol (guided by CARTO system) consisted in two continuous circular lesions around ipsilateral pulmonary veins. Results The following clinical characteristics differed between DM and no-DM patients: age (62.0 ± 10.8 vs. 56.1 ± 10.6 years, P = 0.004), longer AF history (9.6 ± 9.3 vs. 6.7 ± 6.3 years, P = 0.024), significantly larger left atrium size (41.1 ± 7.8 vs. 38.3 ± 5.8 mm, P = 0.021), hypertension (58.1 vs. 35.8%, P = 0.018) and structural heart disease (67.7 vs. 43.5%, P = 0.011). Despite a similar AF recurrence rate in DM and no-DM patients (32.3 vs. 22.4%, P = 0.240), the ablation procedure was complicated in 28 patients (11 hematomas, three cardiac tamponades and three strokes) and the incidence of complications was significantly higher in DM than in no-DM patients (29.0 vs. 8.2%, respectively, P = 0.002). Multivariate analysis showed that DM was an independent risk factor for complications occurrence (odd ratio 5.936, 95% confidence interval 2.059 to 17.112, P = 0.001). Conclusions First catheter ablation of AF procedure in DM patients was equally efficacious than in no-DM patients. However, DM patients had a higher incidence of complications, mostly thrombotic or hemorrhagic.     

PREVIEW (Prevention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World) study in children aged 10 to 17 years: Design,methods and baseline results

Insulin resistance (IR) in adolescence is associated with type 2 diabetes mellitus [T2DM]. The PREVIEW (Prevention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World) study assessed the effectiveness of a high‐protein, low‐glycaemic‐index diet and a moderate‐protein, moderate‐glycaemic‐index diet to decrease IR in insulin‐resistant children who were overweight or obese. Inclusion criteria were age 10 to 17 years, homeostatic model assessment of IR (HOMA‐IR) ≥2.0 and overweight/obesity. In 126 children (mean ± SD age 13.6 ± 2.2 years, body mass index [BMI] z‐score 3.04 ± 0.66, HOMA‐IR 3.48 ± 2.28) anthropometrics, fat mass percentage (FM%), metabolic characteristics, physical activity, food intake and sleep were measured. Baseline characteristics did not differ between the groups. IR was higher in pubertal children with morbid obesity than in prepubertal children with morbid obesity (5.41 ± 1.86 vs 3.23 ± 1.86; P = .007) and prepubertal and pubertal children with overweight/obesity (vs 3.61 ± 1.60, P = .004, and vs 3.40 ± 1.50, P < .001, respectively). IR was associated with sex, Tanner stage, BMI z‐score and FM%. Fasting glucose concentrations were negatively associated with Baecke sport score (r = ?0.223, P = .025) and positively with daytime sleepiness (r = 0.280, P = .016) independent of sex, Tanner stage, BMI z‐score and FM%. In conclusion, IR was most severe in pubertal children with morbid obesity. The associations between fasting glucose concentration and Baecke sport score and sleepiness suggest these might be possible targets for diabetes prevention.     

Pregnancy outcome in patients with raised blood glucose due to a heterozygous glucokinase gene mutation

Aim To assess determinants of fetal growth in the offspring of pregnant women with hyperglycaemia due to a heterozygous glucokinase (GCK) gene mutation. Methods Details of gestational age at delivery, fetal birth weight and maternal antenatal treatment were collected from patients and retrospective case note review of 82 offspring born to 42 women with GCK gene mutations and 31 offspring born to 13 unaffected normoglycaemic women with an affected partner. Fetal genotype was determined using direct sequencing from either a mouth swab or a blood sample. Results In mothers with GCK mutations, non‐mutation‐carrying offspring were heavier than mutation‐carrying offspring (corrected birth weight 3.9 ± 0.6 vs. 3.2 ± 0.8 kg; P < 0.001) and more likely to be macrosomic (> 4.0 kg; 39% vs. 7%, P = 0.001). There was no difference in corrected birth weight between offspring of insulin‐ and diet‐treated women (3.7 ± 0.7 vs. 3.8 ± 0.6 kg; P = 0.1), although insulin‐treated mothers delivered earlier (37.5 ± 1.7 vs. 38.9 ± 2.3 weeks; P < 0.001) due to increased obstetric intervention. Conclusions Offspring of women with GCK mutations are at increased risk of macrosomia and its obstetric consequences. Fetal birth weight is predominantly altered by fetal genotype and not treatment of maternal hyperglycaemia with insulin. This probably reflects the large effect of a fetal GCK mutation on fetal insulin secretion and the difficulty in reducing the regulated maternal glycaemia caused by a glucose sensing defect in people with GCK mutations.     

Coronary anatomy and left ventricular ejection fraction in patients with type 2 diabetes admitted for elective coronary angiography

Patients with diabetes mellitus (DM) have more severe coronary artery disease and a two‐ to fourfold higher risk for myocardial infarction and death as compared to patients without DM. In this study, we analyzed coronary anatomy, left ventricular ejection fraction, and cardiac risk factors in patients with DM referred for coronary angiography and compared them with findings in nondiabetic patients. Coronary anatomy was assessed in a total of 6,234 patients and left ventricular ejection fraction in a subset of 4,767 (76.5%) patients. Diabetic patients (n = 641) were older (60.8 ± 9.6 vs. 58.5 ± 10.5 years; P < 0.0001) and had higher rates of hypertension (65% vs. 47%; P < 0.0001). Three‐vessel disease (DM 44.7% vs. no DM 25.4%; P < 0.0001) and reduced left ventricular ejection fraction (DM 58.4% ± 15.2 vs. no DM 63.9% ± 13.2; P < 0.0001) were significantly associated with DM. After adjustment for age and other vascular risk factors, the presence of DM was associated with a higher atherosclerotic burden. We conclude that advanced coronary heart disease and left ventricular dysfunction are highly prevalent in diabetic patients, independent of age and other cardiovascular risk factors. Thus, cardiac assessment in diabetic patients should, in addition to optimal diabetic control, involve screening for left ventricular dysfunction. Cathet Cardiovasc Intervent 2004;62:432–468. © 2004 Wiley‐Liss, Inc.     

Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers,vascular tone,inflammation, oxidative stress and insulin sensitivity

Objective Current research has focused upon the potential links between novel markers of vascular risk such as endothelial dysfunction, oxidative stress, inflammation and insulin resistance in the pathogenesis of Type 2 diabetes and its complications. Grape seed extract (GSE), a flavonoid‐rich product, is a potential moderator of these markers. This study aimed to test the hypothesis that GSE may improve these markers in high‐risk cardiovascular subjects with Type 2 diabetes. Research design and methods Thirty‐two Type 2 diabetes mellitus patients, prescribed diet or oral glucose‐lowering agents, received GSE (600 mg/day) or placebo for 4 weeks in a double‐blinded randomized crossover trial. Markers of endothelial function (measured by photoplethysmography), oxidative stress [total antioxidant status (TAOS), reduced glutathione (GSH)/oxidized glutathione (GSSG)], inflammation [highly sensitive C‐reactive protein (hsCRP), urinary albumin : creatinine ratio), insulin resistance [homeostasis model assessment–insulin resistance (HOMA–IR)] and metabolism (fructosamine, lipid profile) was measured at baseline and after intervention with GSE or placebo. Results Baseline characteristics (16 male and 16 female): age 61.8 ± 6.36 years; body mass index 30.2 ± 5.92 kg/m²; diabetes duration 5.9 ± 2.14 years. Following GSE (but not placebo), significant changes were noted in fructosamine (282 ± 40.9 vs. 273 ± 50.2 mmol/l; P = 0.0004); whole blood GSH (2359 ± 823 vs. 3595 ± 1051 mmol/l; P < 0.01) and hsCRP (3.2 ± 3.65 vs. 2.0 ± 2.2 mg/l; P = 0.0006). Total cholesterol concentration also decreased (4.5 ± 0.96 vs. 4.3 ± 0.99 mmol/l; P = 0.05). No statistically significant changes were shown in endothelial function, HOMA–IR or TAOS. Conclusion GSE significantly improved markers of inflammation and glycaemia and a sole marker of oxidative stress in obese Type 2 diabetic subjects at high risk of cardiovascular events over a 4‐week period, which suggests it may have a therapeutic role in decreasing cardiovascular risk.     

Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study

The relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassaemia major (TM). We evaluated a large retrospective historical cohort of TM to determine whether DM is associated with a higher risk of heart complications. We compared 86 TM patients affected by DM with 709 TM patients without DM consecutively included in the Myocardial Iron Overload in Thalassaemia database where clinical/instrumental data are recorded from birth to the first cardiovascular magnetic resonance (CMR) exam. All of the cardiac events considered were developed after the DM diagnosis. In DM patients versus non‐DM patients we found a significantly higher frequency of cardiac complications (46·5% vs. 16·9%, P < 0·0001), heart failure (HF) (30·2% vs. 11·7%, P < 0·0001), hyperkinetic arrhythmias (18·6% vs. 5·5%, P < 0·0001) and myocardial fibrosis assessed by late gadolinium enhancement (29·9% vs. 18·4%, P = 0·008). TM patients with DM had a significantly higher risk of cardiac complications [odds ratio (OR) 2·84, P < 0·0001], HF (OR 2·32, P = 0·003), hyperkinetic arrhythmias (OR 2·21, P = 0·023) and myocardial fibrosis (OR 1·91, P = 0·021), also adjusting for the absence of myocardial iron overload assessed by T2* CMR and for the covariates (age and/or endocrine co‐morbidity). In conclusion, DM significantly increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis in TM patients.     

No survival benefit associated with routine surveillance imaging for Hodgkin lymphoma in first remission: a Danish‐Swedish population‐based observational study

The use of routine imaging for patients with classical Hodgkin lymphoma (HL) in complete remission (CR) is controversial. In a population‐based study, we examined the post‐remission survival of Danish and Swedish HL patients for whom follow‐up practices were different. Follow‐up in Denmark included routine imaging, usually for a minimum of 2 years, whereas clinical follow‐up without routine imaging was standard in Sweden. A total of 317 Danish and 454 Swedish comparable HL patients aged 18–65 years, diagnosed in the period 2007–2012 and having achieved CR following ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) therapy, were included in the study. The cumulative progression rates in the first 2 years were 4% (95% confidence interval [CI] 1–7) for patients with stage I–II disease vs. 12% (95% CI 6–18) for patients with stage III–IV disease. An imaging‐based follow‐up practice was not associated with a better post‐remission survival in general (P = 0·2) or in stage‐specific subgroups (P = 0·5 for I–II and P = 0·4 for III–IV). Age ≥45 years was the only independent adverse prognostic factor for survival. In conclusion, relapse of HL patients with CR is infrequent and systematic use of routine imaging in these patients does not improve post‐remission survival. The present study supports clinical follow‐up without routine imaging, as encouraged by the recent Lugano classification.     

Comparison of maternal ghrelin and leptin in healthy mothers and mothers with Type 1 diabetes

Aims Maternal leptin affects placental growth hormone (GH), whereas ghrelin, a natural ligand of the growth‐hormone‐secretagogue receptor, modulates GH action. Both hormones may affect fetal growth, and dysregulation in diabetes may lead to fetal growth disturbances. The aim was to investigate changes in maternal ghrelin during pregnancy with diabetes and to establish reference leptin levels. Methods Twelve healthy non‐diabetic (ND) and 12 pregnant women with Type 1 diabetes (T1DM) were recruited. Age and body mass index (BMI) [ND: age 29.9 ± 4.7 years (mean ± sd ), BMI 25.2 ± 3.7 kg/m²; T1DM: age 31 ± 5.5 years, BMI 27 ± 3.1 kg/m²] were similar in the groups. HbA_1c in T1DM was 6.2 ± 1.1% at 20 weeks, 6.3 ± 1.1% at 30 weeks’ gestation and 7.8 ± 2.1% postpartum. Fasting plasma ghrelin, total leptin, free leptin (FL) and soluble leptin receptor (sOB‐R) levels were measured at 20 and 30 weeks’ gestation and postpartum and determined by radioimmunoassay. Results All pregnancies resulted in full‐term singleton births with no differences in birth weight between groups [T1DM: 3.4 ± 0.56 kg (mean ± SE); ND: 3.6 ± 0.3 kg, P = NS]. Ghrelin levels were lower in T1DM when corrected for age and mothers’ weight (T1DM: 458 ± 36 pg/ml and 432.9 ± 26.6 pg/ml; ND: 562 ± 52 pg/ml and 515.8 ± 63 pg/ml at 20 and 30 weeks, respectively, P < 0.05). T1DM mothers had higher levels of sOB‐R and FL levels declined at 30 weeks’ gestation in T1DM (P = 0.04) but not in ND. Conclusion In a population of pregnant women with expected changes in leptin levels as previously reported, ghrelin levels were lower in T1DM pregnancies at 20 and 30 weeks. This may have implications for fetal development and requires further study in diabetes, particularly in pregnancies that result in macrosomia.     

Prevalence and clinical characteristics of maternally inherited diabetes and deafness caused by the mt3243A > G mutation in young adult diabetic subjects in Sri Lanka

Aims The maternally inherited mt3243A > G mutation is associated with a variable clinical phenotype including diabetes and deafness (MIDD). We aimed to determine the prevalence and clinical characteristics of MIDD in a large South Asian cohort of young adult‐onset diabetic patients from Sri Lanka. Methods DNA was available from 994 subjects (age of diagnosis 16–40 years, age at recruitment ≤ 45 years). Mutation screening was performed using a QRT‐PCR method on an ABI 7900HT system using sequence‐specific probes. Samples with heteroplasmy ≥ 5.0% were considered positive. Results Nine (four males) mutation‐positive subjects were identified (prevalence 0.9%). They were diagnosed at a younger age (25.9 ± 4.8 years vs. 31.9 ± 5.6 years, P = 0.002) and were lean (body mass index [BMI] 18.7 ± 2.7 kg/m² vs. 24.7 ± 4.0 kg/m², P < 0.001) compared to NMCs. One mutation‐positive subject (11.1%) had metabolic syndrome, compared to 633 (64.3%) of NMCs. Insulin therapy within 6 months of diagnosis was used in four (44.0%) carriers compared to 6.9% of NMCs (P = 0.002). Combined screening criteria of any two of maternal history of diabetes, personal history of hearing impairment and family history of hearing impairment only identified five (55%) of the carriers, with a positive predictive value of 7.4%. Conclusions The prevalence of mt3243A > G mutation among young adult‐onset diabetic subjects from Sri Lanka was 0.9%. Our study demonstrates that a maternal family history of diabetes and either a personal and/or family history of deafness only distinguish half of patients with MIDD from Sri Lankan subjects with young‐onset diabetes.     

Immigration to Israel during childhood is associated with diabetes at adolescence: a study of 2.7 million adolescents

Aims/hypothesis

Immigration studies can shed light on diabetes pathogenesis and risk factors. To this end, we investigated the association between age at immigration and diabetes occurrence at adolescence among immigrants to Israel.

Methods

We analysed cross-sectional data on 2,721,767 Jewish adolescents assessed for mandatory military service at approximately 17 years of age between 1967 and 2014. The study population comprised 430,176 immigrants with origins in Ethiopia, former USSR, Middle East and North Africa (ME/NA) and western countries. ORs for diabetes were calculated for men and women, grouped according to age at immigration, with Israel-born participants as controls. Unadjusted and fully adjusted models were made to account for possible confounders. Additionally, the study population was stratified by origin and each immigrant group was referenced to Israel-born participants of the same origin.

Results

There was a graded decrease in OR for diabetes across the study groups in the fully adjusted model. Immigrants arriving at age 0–5 years had comparable OR for diabetes to the Israeli-born reference group; those arriving at age 6–11 years had an OR of 0.82 (95% CI 0.70, 0.97; p = 0.017) and recent immigrants, arriving at age 12–19 years, had the lowest OR of 0.65 (95% CI 0.54, 0.77; p < 0.0001). When age at immigration was treated as a continuous variable, there was an adjusted risk for occurrence of diabetes of 0.97 (95% CI 0.96, 0.99; p = 0.001) for every year increment. The lower risk for diabetes among recent immigrants persisted in the unadjusted model and persisted when the study sample was stratified by sex and origin, except for immigrants arriving from ME/NA. Notably, Ethiopians born in Israel had a sixfold higher diabetes crude prevalence than Ethiopian immigrants arriving after the age of 5 years.

Conclusions/interpretation

Immigrants of different ethnic groups arriving earlier in childhood lose their protection against diabetes at adolescence, relative to children born in Israel. This is perhaps due to environmental and lifestyle changes, especially those beginning at an early age.

     

Handedness,insulin sensitivity and pancreatic B‐cell function in Type 2 diabetes

Background Laterality is associated with various health conditions. No study has addressed the influence of handedness on Type 2 diabetes mellitus (T2DM) phenotype, including glucose homeostasis, glucose‐lowering therapies and metabolic control. Methods Five hundred and seventy‐six consecutive adult T2DM outpatients underwent homeostasis model assessment (HOMA) of pancreatic B‐cell function (B), insulin sensitivity (S), hyperbolic product (B × S) and age‐standardized B × S deficit. Right‐handed patients (87.5%; RH; n = 504) had similar age, gender, diabetes duration and education than non‐right‐handed patients (12.5%; non‐RH; n = 72). Results Non‐RH were more insulin‐sensitive: 66% (39%) vs. 52% (36%) [mean (1 sd ); P = 0.0024] and had significantly higher B × S and lower age‐adjusted B × S deficit: 35% (20%) vs. 26% (17%) and 1.08% (0.40%) vs. 1.32% (0.55%)/year (non‐RH; P = 0.0005 and P < 0.0001, respectively). Conclusions Non‐right‐handed T2DM patients are more insulin‐sensitive, have higher hyperbolic product and less age‐standardized B × S deficit. These may modulate glucose‐lowering therapy requirements and glycaemic control.