Distribution of IL-1β immunoreactive cells in pancreatic biopsies from living volunteers with new-onset type 1 diabetes: comparison with donors without diabetes and with longer duration of disease

Aims/hypothesis

Although IL-1β is considered a key mediator of beta cell destruction, its cellular expression in islets during early type 1 diabetes remains unclear. We compared its expression in rare pancreatic biopsies from new-onset living volunteers with its expression in cadaveric pancreas sections from non-diabetic autoantibody-positive and -negative individuals and those with long-standing disease.

Methods

Pancreatic biopsy sections from six new-onset living volunteers (group 1) and cadaveric sections from 13 non-diabetic autoantibody-negative donors (group 2), four non-diabetic autoantibody-positive donors (group 3) and nine donors with diabetes of longer duration (0.25–12 years of disease; group 4) were triple-immunostained for IL-1β, insulin and glucagon. Intra- and peri-islet IL-1β-positive cells in insulin-positive and -negative islets and in random exocrine fields were enumerated.

Results

The mean number of IL-1β-positive cells per islet from each donor in peri- and intra-islet regions was <1.25 and <0.5, respectively. In all study groups, the percentage of islets with IL-1β cells in peri- and/or intra-islet regions was highly variable and ranged from 4.48% to 17.59% in group 1, 1.42% to 44.26% in group 2, 7.93% to 17.53% in group 3 and 3.85% to 42.86% in group 4, except in a single case where the value was 75%. In 25/32 donors, a higher percentage of islets showed IL-1β-positive cells in peri-islet than in intra-islet regions. In sections from diabetic donors (groups 1 and 4), a higher mean number of IL-1β-positive cells occurred in insulin-positive islets than in insulin-negative islets. In group 2, 70–90% of islets in 3/13 sections had weak-to-moderate IL-1β staining in alpha cells but staining was virtually absent or substantially reduced in the remaining groups. The mean number of exocrine IL-1β-positive cells in group 1 was lower than in the other groups.

Conclusions/interpretation

At onset of type 1 diabetes, the low number of islet-associated IL-1β-positive cells may be insufficient to elicit beta cell destruction. The variable expression in alpha cells in groups 2–4 suggests their cellular heterogeneity and probable physiological role. The significance of a higher but variable number of exocrine IL-1β-positive cells seen in non-diabetic individuals and those with long-term type 1 diabetes remains unclear.

     

Toe–brachial index as a predictor of cardiovascular disease and all-cause mortality in people with type 2 diabetes and microalbuminuria

Aims/hypothesis

The study aimed to evaluate toe–brachial index (TBI) and ankle–brachial index (ABI) as determinants of incident cardiovascular disease (CVD) and all-cause mortality in people with type 2 diabetes and microalbuminuria.

Methods

This was a prospective study including 200 participants. Unadjusted and adjusted (traditional risk factors and additional inclusion of N-terminal pro-brain natriuretic peptide [NT-proBNP] and coronary artery calcification) Cox regression models were performed. C statistics and relative integrated discrimination improvement (rIDI) evaluated risk prediction improvement.

Results

Median follow-up was 6.1 years; 40 CVD events and 26 deaths were recorded. Lower TBI was associated with increased risk of CVD (HR per 1 SD decrease: 1.55 [95% CI 1.38, 1.68]) and all-cause mortality (1.41 [1.22, 1.60]) unadjusted and after adjustment for traditional risk factors (CVD 1.50 [1.27, 1.65] and all-cause mortality 1.37 [1.01, 1.60]). Lower ABI was a determinant of CVD (1.49 [1.32, 1.61]) and all-cause mortality (1.37 [1.09, 1.57]) unadjusted and after adjustment for traditional risk factors (CVD 1.44 [1.23, 1.59] and all-cause mortality 1.39 [1.07, 1.60]). After additional adjustment for NT-proBNP and coronary artery calcification, lower TBI remained a determinant of CVD (p = 0.023). When TBI was added to traditional risk factors, the AUC increased significantly for CVD, by 0.063 (95% CI 0.012, 0.115) from 0.743 (p = 0.016), but not for all-cause mortality; adding ABI did not improve the AUC significantly. The rIDI for TBI was 46.7% (p < 0.001) for CVD and 46.0% (p = 0.002) for all-cause mortality; for ABI, the rIDI was 51.8% (p = 0.004) for CVD and 53.6% (p = 0.031) for all-cause mortality.

Conclusions/interpretation

Reduced TBI and ABI were associated with increased risk of CVD and all-cause mortality, independent of traditional risk factors in type 2 diabetes, and improved prognostic accuracy.

     

Hyposplenism in alcoholic cirrhosis,facts or artifacts? A comparative analysis with non‐alcoholic cirrhosis and extrahepatic portal venous obstruction

BACKGROUND AND AIMS: Hyposplenism has been described in patients with alcoholic cirrhosis (AC). However, no data are available regarding hyposplenism in patients with non-alcoholic cirrhosis (NAC) and other forms of portal hypertension such as extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic functions in patients with AC, NAC, and EHPVO. METHODS: Splenic functions were assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO. The tests included pitted red blood cells (RBC; %) and Howell-Jolly bodies in the peripheral smear. Pitted RBCs > 2% with or without the presence of Howell-Jolly bodies were taken as indicators of hyposplenism. The splenic function in each group was compared with age-matched controls. RESULTS: Hyposplenism was found in 10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO. The mean pitted RBCs were significantly increased in patients with AC (mean 4.93 +/- 1.36% vs control 1.22 +/- 0.17%, P < 0.05), but not so with NAC (2.01 +/- 0.69%) and EHPVO (mean 0.99 +/- 0.1% vs control 0.66 +/- 0.1%, P > 0.05). Howell-Jolly bodies were seen in only four patients. The mean pitted RBCs were significantly higher among patients who were actively consuming alcohol (9.14 +/- 3.35%) compared to those who abstained at least for more than 24 weeks (2.0 +/- 1.3%, P < 0.05). CONCLUSION: Hyposplenism is more common in AC patients, particularly those who are actively consuming alcohol compared with those who abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO patients, it is uncommon.     

Is low birth weight a risk factor for the development of diabetic nephropathy in patients with type 1 diabetes? A population‐based case–control study

OBJECTIVES: To investigate if low birth weight as a consequence of intrauterine malnutrition is a risk factor for the later development of diabetic nephropathy. DESIGN AND SUBJECTS: In a case-control set-up a group of type 1 diabetic subjects with diabetic nephropathy (n = 51) and a matched control group with normal kidney function (n = 51) were compared. Diabetic nephropathy and normal kidney function were defined as urinary albumin excretion rate above 200 microg min-1 and below 20 microg min-1, respectively. The birth weights were all obtained from the midwives' original records. SETTING: The patients were identified from a population-based study of chronic diabetic complications in the Funen County, Denmark. MAIN OUTCOMES: Birth weights according to the presence of diabetic nephropathy. RESULTS: The median (10-90 percentile) birth weights were 3,600 g (2,960-4,274) in the group with diabetic nephropathy and 3,600 g (2,880-4,220) in the group without nephropathy, P = 0.52. In the lower quartile of birth weights the median (10-90 percentile) birth weights were 3,000 g (2,780-3,200) in the group with nephropathy versus 2,850 g (2,250-3,175) in the group without nephropathy, P = 0.07. In the upper quartile the median (10-90 percentile) birth weights were 4,225 g (4,000-4,741) in the nephropathy group and 4,000 g in the group without nephropathy, P = 0.13. We found no significant correlation between birth weights and log urinary albumin excretion rate (r = 0.148, P = 0.14) and no difference in the number of patients with nephropathy in the lower versus upper quartiles of birth weights. CONCLUSION: We found no evidence of low birth weight as a risk factor for the development of diabetic nephropathy.     

Association of BMI with cardiovascular disease incidence and mortality in patients with type 2 diabetes mellitus: A systematic review and dose–response meta-analysis of cohort studies

AimsThe relation of body mass index (BMI) with cardiovascular disease (CVD) and mortality has been extensively investigated in the general population but is less clear in individuals with type 2 diabetes mellitus (T2DM). We performed a meta-analysis of cohort studies to quantitatively evaluate the association of BMI with CVD incidence and mortality in patients with T2DM.Data synthesisPubMed and Embase databases were searched for relevant cohort articles published up to June 8, 2020. Restricted cubic splines were used to evaluate the potential linear or non-linear dose–response associations. We identified 17 articles (21 studies) with 1,349,075 participants and 57,725 cases (49,354 CVD incidence and 8371 CVD mortality) in the meta-analysis. We found a linear association between BMI and risk of CVD incidence (P_{non-linearity} = 0.182); the pooled RR for CVD incidence was 1.12 (95% CI, 1.04–1.20) with a 5-unit increase in BMI. We found an overall nonlinear relationship between BMI and CVD mortality (P_{non-linearity} < 0.001). The lowest risk was at BMI about 28.4 kg/m², with increased mortality risk for higher BMI values; the RR with a 5-unit increase in BMI was 0.87 (95% CI, 0.79–0.96) and 1.11 (95% CI, 1.04–1.18) for BMI ≤28.4 kg/m² and BMI >28.4 kg/m², respectively.ConclusionsIn individuals with T2DM, BMI may have a positive linear association with risk of CVD incidence but a nonlinear association with CVD mortality. Our results can provide evidence for weight control and lifestyle intervention for preventing and managing cardiovascular disease in T2DM.     

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

Aims/hypothesis  Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima–media thickness (CIMT). Methods  We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured. Results  CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46–69%; p = 0.004–0.043). In people with type 1 diabetes, FMD was reduced by 45% (p < 0.001) and CIMT increased by 25% (p < 0.001), these being correlated (r = −0.25, p = 0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r = 0.25, p = 0.037) and CD34+ (r = 0.34, p = 0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r = −0.27, p = 0.028 and r = −0.24, p = 0.048, respectively). Conclusions/interpretation  These findings suggest that abnormalities of endothelial function in addition to pro-inflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Knowledge,attitudes and practices with regard to sugar sweetened beverages and taxation among people with type 2 diabetes mellitus in the Caribbean island of Barbados – A cross sectional survey in primary care

AimsBarbados implemented a 10% tax on sugar sweetened beverages (SSBs) in 2015. We aimed to determine knowledge, attitudes and practices towards SSB consumption and taxation among people with type 2 diabetes (T2D) attending public sector primary care clinics in Barbados.MethodsPeople with T2D attending public sector clinics completed a survey including the Beverage Intake Questionnaire (BEVQ-15). Waist circumference was measured.ResultsOf 384 participants (34.6% male, median age 67 years, interquartile range 60–74 years, African descent 97.6%) 45.9% had diabetes diagnosed for >10 years, 30.7% used insulin, 31.8% had not seen a dietician since diabetes diagnosis, and 62.2% had abdominal obesity. Most (91.1%) thought that consuming SSB was unhealthy and 91% felt that reducing intake would be easy. Only 44.7% favoured the current 10% tax and 29.7% favoured a 20% tax. The median daily SSB consumption was 26.6 ml (IQR 3.0–53.2). Responses did not differ by age, gender or abdominal obesity status (p > 0.5). Weight loss was being attempted by 45.6% and 21.1% with and without abdominal obesity respectively (p < 0.0001).ConclusionsWhile most felt SSB consumption is harmful and the median reported consumption contributes few calories to the diet, a minority supported the current tax.     

Down’s syndrome in diabetic patients aged <20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes

Aims/hypothesis  

Intellectual impairment in individuals with Down’s syndrome and diabetes mellitus potentially limits the quality of diabetic control. In addition, these patients are at risk of having immunological abnormalities. The present study compared metabolic status and concomitant diseases in young (<20 years old) Down’s syndrome patients with diabetes vs young type 1 diabetic patients.     

Can procalcitonin tests aid in identifying bacterial infections associated with influenza pneumonia? A systematic review and meta‐analysis

Objective To summarize evidence for the diagnostic accuracy of procalcitonin (PCT) tests for identifying secondary bacterial infections in patients with influenza. Methods Major databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched for studies published between January 1966 and May 2009 that evaluated PCT as a marker for diagnosing bacterial infections in patients with influenza infections and that provided sufficient data to construct two‐by‐two tables. Results Six studies were selected that included 137 cases with bacterial coinfection and 381 cases without coinfection. The area under a summary ROC curve was 0·68 (95% CI: 0·64–0·72). The overall sensitivity and specificity estimates for PCT tests were 0·84 (95% CI: 0·75–0·90) and 0·64 (95% CI: 0·58–0·69), respectively. These studies reported heterogeneous sensitivity estimates ranging from 0·74 to 1·0. The positive likelihood ratio for PCT (LR+ = 2·31; 95% CI: 1·93–2·78) was not sufficiently high for its use as a rule‐in diagnostic tool, while its negative likelihood ratio was reasonably low for its use as a rule‐out diagnostic tool (LR? = 0·26; 95% CI: 0·17–0·40). Conclusions Procalcitonin tests have a high sensitivity, particularly for ICU patients, but a low specificity for identifying secondary bacterial infections among patients with influenza. Because of its suboptimal positive likelihood ratio and good negative likelihood ratio, it can be used as a suitable rule‐out test but cannot be used as a standalone rule‐in test.