Type 2 Diabetes Complications Research Articles

Bone mineral density progression following long-term simultaneous pancreas-kidney transplantation in type-1 diabetes

IntroductionSimultaneous pancreas-kidney transplantation (SPKT) has demonstrated favorable impact on the progression of chronic complications in type-1 diabetes (T1D) and terminal chronic kidney disease (CKD). However, some CKD mineral and bone disorders (CKD-MBD) may persist, even after transplantation. There are only a few studies addressing the long-term progression of bone mineral density (BMD) in these patients. Our aim was to assess baseline BMD and long-term progression and consequences in patients with T1D undergoing SPKT. MethodsA retrospective cohort included patients undergoing SPKT in our tertiary center between 2000 and 2017. BMD progression was assessed on dual X-ray absorptiometry (DXA). Only patients with baseline data and a minimum follow-up of 2 years were included. ResultsSeventy-three patients were included, 53.4% male, with a median age at SPKT of 35 years (interquartile range [IQR] 31; 39). At transplantation, the median T-scores for the lumbar spine (LS) and femoral neck (FN) were −1.6 (IQR −2.6; −1.1) and -−2.1 (IQR −2.7; −1.6), respectively. Seventy-five percent of patients presented low BMD (osteopenia or osteoporosis) in the LS and 90% in the FN, with 33% osteoporosis in the LS and 36% in the FN. On multivariate analysis, male gender (odds ratio [OR] 10.82, 95% confidence interval (CI) 2.88–40.70) and low body-mass index (BMI) (OR 0.73, 95% CI 0.55–0.97) were significantly associated with lumbar but not femoral osteoporosis. At long-term follow-up, BMD significantly improved in the LS (ΔT-score +0.41, P<0.001) and FN (ΔT-score +0.29, P=0.01), at a median 4 years after SPKT. Twelve (16.4%) and 9 (12.3%) patients showed persistent FN and LS osteoporosis, respectively. Multivariate linear regression showed that high BMI was predictive of improvement in BMD. ConclusionsThis study demonstrated severe skeletal fragility in T1D patients with terminal CKD undergoing SPKT, more than a quarter of whom showed osteoporosis. The significant improvement in BMD may result from metabolic correction by SPKT and from physiological skeleton mineralization, which continues in this age group. BMD progression was positively associated with BMI, due to improved nutritional balance after transplantation.

Epigenetics in Obesity and Diabetes Mellitus: New Insights

A long-term complication of obesity is the development of type 2 diabetes (T2D). Patients with T2D have been described as having epigenetic modifications. Epigenetics is the post-transcriptional modification of DNA or associated factors containing genetic information. These environmentally-influenced modifications, maintained during cell division, cause stable changes in gene expression. Epigenetic modifications of T2D are DNA methylation, acetylation, ubiquitylation, SUMOylation, and phosphorylation at the lysine residue at the amino terminus of histones, affecting DNA, histones, and non-coding RNA. DNA methylation has been shown in pancreatic islets, adipose tissue, skeletal muscle, and the liver. Furthermore, epigenetic changes have been observed in chronic complications of T2D, such as diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. Recently, a new drug has been developed which acts on bromodomains and extraterminal (BET) domain proteins, which operate like epigenetic readers and communicate with chromatin to make DNA accessible for transcription by inhibiting them. This drug (apabetalone) is being studied to prevent major adverse cardiovascular events in people with T2D, low HDL cholesterol, chronic kidney failure, and recent coronary events. This review aims to describe the relationship between obesity, long-term complications such as T2D, and epigenetic modifications and their possible treatments.

Real-World Diabetes Technology: Overcoming Barriers and Disparities.

Real-World Diabetes Technology: Overcoming Barriers and Disparities.

Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant.

Type 1 diabetes patients carrying a 'protective' insulin gene (INS) variant present a disease endotype with reduced insulin antibody titers, preserved beta cell function and improved glycemic control. We tested whether this protective INS variant associated with lowered risk for development of proliferative diabetic retinopathy (PDR) and diabetic kidney disease (DKD) as long-term diabetic complications. Insulin gene polymorphisms were evaluated in 1,363 type 1 diabetes patients participating in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study that compared intensive versus conventional insulin therapy in relation with development of PDR and DKD with a follow-up of over two decades. PDR and DKD were absent in type 1 diabetes patients carrying the protective INS variant and receiving intensive insulin therapy (the current standard of clinical care) 1-5 years from their diagnosis (n = 67; mean post-diagnosis follow up of 20.4 ± 1.6 years), versus 11 of 258 patients (4.3%) lacking this variant (20.4 ± 1.8 years follow up). In the secondary intervention group of the intensive therapy arm (1-15 years of disease), PDR was significantly less frequent in carriers of the protective INS variant than those without it (4 of 83 [4.8%] vs. 31 of 260 [11.9%]; p = 0.032; 26.1 ± 3.9 and 26.3 ± 4.1 years follow-up, respectively), whereas DKD frequencies were no different between those with or without this variant (5 of 83 [6.0%] vs. 11 of 260 [4.2%]). Carrying a copy of this protective INS variant further reduces the risk of diabetic complications achieved by intensive insulin therapy and marks a disease endotype with superior glycemic control, increased and extended beta cell function, and prevention of DKD and PDR.

High prevalence of cardiovascular disease and risk factors among type 2 diabetes patients followed in a hospital setting in Portugal: The PICT2RE observational study

Introduction and ObjectivesPortugal is a country with a high prevalence of type 2 diabetes (T2D) and cardiovascular disease (CVD). The prevalence of CVD and cardiovascular (CV) risk factors among T2D patients followed in hospitals in Portugal is not known. The primary objective of this study was to assess the prevalence of CVD and CV risk factors among T2D patients in a hospital setting in Portugal. The clinical management of CVD in the hospital setting was also assessed. MethodsWe performed a non-interventional, multicenter, cross-sectional study with a retrospective phase. T2D patients were consecutively invited to participate. Data were collected retrospectively. ResultsA total of 715 patients were included in the study. Mean age and diabetes duration were 66.6 and 17.4 years, respectively. Of these, 286 patients (40.0%) had been diagnosed with CVD, mostly ischemic heart disease (50.4%). All patients had at least one CV risk factor. CVD was significantly associated with hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol, hypertriglyceridemia and smoking. During the three years prior to study inclusion, the incidence of hyperglycemic episodes and T2D complications increased among patients with established CVD, but the numbers of hospitalization episodes and specialist appointments remained stable. An improvement was observed in key cardiometabolic risk factors. ConclusionsOur study revealed a high prevalence of CVD and CV risk factors among a sample of T2D patients in a hospital setting. Patients with established CVD seem to be adequately managed but further efforts are needed at the prevention stage for better control of risk factors and morbidity.

A Pilot Study to Assess Effect of Metformin Therapy on Prevention of Double Diabetes in Indian Adolescents with Type-1 Diabetes.

Increased prevalence of metabolic syndrome in Indian adolescents owing to the obesity epidemic leads to double diabetes (DD), which is associated with an increased risk of complications in type-1 diabetes (T1D). Metformin may be a useful intervention for the prevention and treatment of insulin resistance in T1D. We conducted this pilot randomized controlled trial with the objective of investigating the effect of metformin on insulin sensitivity in Indian adolescents with T1D. This pilot randomized controlled trial was performed on 59 participants with T1D aged 10-19 years distributed uniformly by gender and puberty across two groups with a 3-month intervention period. The intervention group received metformin (weight less than 60 kg received 500 mg twice daily and more than 60 kg received 1 gm twice daily) and non-metformin group received standard of care for diabetes. Anthropometric, clinical details, biochemistry and insulin sensitivity indices (ISI) were evaluated using standard protocols at baseline and endline. 22.2% of subjects from non-metformin group and 12.5% from metformin group were at the risk of the development of DD. The odds ratio and relative risk for the development of DD in non-metformin subjects were 2.0 and 1.4, respectively, as compared to participants in metformin group. The mean improvement in ISI ranged from 1.4% to 4.6% in participants on metformin as opposed to deterioration of -2% to -14.1% in non-metformin group. On performing the paired sample t-test, the reduction in ISI in non-metformin group was significant. Metformin may prevent deterioration in insulin sensitivity in Indian adolescents with T1D.

Paraoxonase 1 Activity is Associated with Interleukin-6 Levels in Type 2 Diabetes: Effects of Age and Gender.

A further understanding of the mechanisms linking inflammation to T2D and related complications can help prevent or control this silent but dangerous disease. This study was conducted to determine the association between paraoxonase 1 (PON1) activity and interleukin-6 (IL-6) in type 2 diabetes (T2D). Furthermore, we have evaluated the role of age and gender in the relationship between the PON1 activity and IL-6. A total of 105 people with T2D were enrolled in this study. IL-6 levels were determined using ELISA. For the PON1 activity assay, the hydrolysis rate of the substrate phenylacetate was spectrophotometrically assayed in serum at 270 nm. The determined velocities were the initial velocities of substrate hydrolysis. PON1 activity was negatively correlated with IL-6 in total data (r = -0.34, P = 0.001). In both groups with age ≥50 and <50 years, PON1 activity was negatively correlated with IL-6, but the correlation was significant in patients aged 50 years and above (r = -0.358, P = 0.005) compared with patients with age <50 years. In both women and men, PON1 activity was negatively correlated with IL-6, but the correlation was significant in women (r = -0.318, P = 0.006) in comparison with men. Inverse association between PON1 activity and IL-6 in T2D may represent the oxidative-inflammatory interaction in this disease. Our findings highlight that at older ages and in women, the associations between lower PON1 activity and higher IL-6 concentrations are more evident, and this should be considered in patients with T2D.

Health system capacity to manage diabetic ketoacidosis in nine low-income and lower-middle income countries: A cross-sectional analysis of nationally representative survey data.

There has been increasing awareness about the importance of type 1 diabetes (T1D) globally. Diabetic ketoacidosis (DKA) is a life-threatening complication of T1D in low-income settings. Little is known about health system capacity to manage DKA in low- and lower-middle income countries (LLMICs). As such, we describe health system capacity to diagnose and manage DKA across nine LLMICs using data from Service Provision Assessments. In this cross-sectional study, we used data from Service Provision Assessment (SPA) surveys, which are part of the Demographic and Health Survey (DHS) Program. We defined an item set to diagnose and manage DKA in higher-level (tertiary or secondary) facilities, and a set to assess and refer patients presenting to lower-level (primary) facilities. We quantified each item's availability by service level in Bangladesh (Survey 1: May 22 2014-Jul 20 2014; Survey 2: Jul 2017-Oct 2017), the Democratic Republic of the Congo (DRC) (Oct 16 2017-Nov 24 2017 in Kinshasha; Aug 08 2018-Apr 20 2018 in rest of country), Haiti (Survey 1: Mar 05 2013-Jul 2013; Survey 2: Dec 16 2017-May 09 2018), Ethiopia (Feb 06 2014-Mar 09 2014), Malawi (Phase 1: Jun 11 2013-Aug 20 2013; Phase 2: Nov 13 2013-Feb 7 2014), Nepal (Phase 1: Apr 20 2015-Apr 25 2015; Phase 2: Jun 04 2015-Nov 05 2015), Senegal (Survey 1: Jan 2014-Oct 2014; Survey 2: Feb 09 2015-Nov 10 2015; Survey 3: Feb 2016-Nov 2016; Survey 4: Mar 13 2017-Dec 15 2017; Survey 5: Apr 15 2018-Dec 31 2018; Survey 6: Apr 15 2019-Feb 28 2020), Tanzania (Oct 20 2014-Feb 21 2015), and Afghanistan (Nov 1 2018-Jan 20 2019). Variation in secondary facilities' capacity and trends over time were also explored. We examined data from 2028 higher-level and 7534 lower-level facilities. Of these, 1874 higher-level and 6636 lower-level facilities' data were eligible for analysis. Availability of all item sets were low at higher-level facilities, where less than 50% had the minimal set of supplies, less than 20% had the full minimal set, and less than 15% had the ideal set needed to diagnose and manage DKA. Across countries in lower-level facilities, less than 14% had the minimal set of supplies and less than 9% the full set of supplies for diagnosis and transfer of DKA patients. No country had more than 20% of facilities with the minimal set of items needed to assess or manage DKA. Where data were available for more than one survey (Bangladesh, Senegal, and Haiti), changes in availability of the minimal set and ideal set of items did not exceed 15%. Tertiary facilities performed best in Haiti, Ethiopia, Malawi, Nepal, Senegal, Tanzania, and Afghanistan. Secondary facilities that were rural, public, and had fewer staff had lower capacity. Health system capacity to manage DKA was low across these nine LLMICs. Although efforts are underway to strengthen health systems, a specific focus on DKA management is still needed. Leona M. and Harry B. Helmsley Charitable Trust, and Juvenile Diabetes Research Foundation Ltd.

Povezanost polimorfizama PON1 i APOE sa nivoima lipida u plazmi i rizikom od kasnih komplikacija kod pacijenata sa dijabetesom tipa 2

Background: Besides good glycemic control, also control of lipid levels can effectively prevent or delay late type 2 diabetes (T2D) complications. As apolipoprotein E (APOE) and paraoxonase 1 (PON1) were shown to suppress atherosclerosis, we investigated the associations of common functional PON1 and APOE polymorphisms with plasma lipid levels and the risk for late complications in T2D patients. Methods: Our retrospective genetic association study included 181 T2D patients genotyped for PON1 rs622, PON1 rs854560, APOE rs429358 and APOE rs7412. Results: PON1 rs622 G allele carriers had significantly lower LDL-C (p=0.024) and lower LDL/HDL ratio (p=0.031) under recessive model. Also in the subgroup of statin treated patients, PON1 rs622 G allele carriers had significantly lower LDL-C (p=0.019), lower total cholesterol/LDL ratio (0.043) and lower LDL/HDL ratio (0.009) when compared to noncarriers. After adjustment for clinical characteristics only associations of PON1 rs622 with macrovascular complications (p=0.002) and MI (p=0.041) remained significant. PON1 rs854560 and APOE genotypes were not associated with late T2D complications. Conclusion: Although our data show some associations between PON1 polymorphisms and lipid levels in T2D patients, as well as with late T2D complications, these associations do not seem to be clinically relevant in T2D patients.

SISTER (Sisters Inspiring Sisters to Engage in Relevant Diabetes Self-Care) Diabetes Study: Protocol for diabetes medical nutrition therapy randomized clinical trial among African American women

BackgroundAfrican American (AA) women with type 2 diabetes (T2D) carry disproportionate diabetes-related morbidity and mortality burdens. Diabetes medical nutrition therapy (MNT) improves glycemic, blood pressure, and cholesterol control, all critical in preventing and reducing diabetes complications. Yet, MNT does not address low motivation for dietary intake management, which is frequently reported among AA women with T2D living in the Southeastern US. MethodsA randomized controlled trial will be used to test the central hypothesis that diabetes MNT plus culturally-tailored motivational interviewing (MI) (diabetes MNT plus MI) is more effective than diabetes MNT alone (diabetes MNT). Two hundred ninety-one Southeastern AA women who are at risk for development and/or progression of T2D complications will be randomized to diabetes MNT plus MI or diabetes MNT. Both groups will include: 1) a 3-month active intervention period, consisting of group-based, nutritionist-facilitated MNT sessions; 2) a 3-month maintenance intervention period, including one group-based, nutritionist-facilitated maintenance support session; and 3) a 6-month inactive period. Culturally-adapted MI exercises will be integrated into the diabetes MNT plus MI group only. Primary (HbA1c) and secondary (systolic blood pressure, LDL cholesterol) outcomes will be assessed at baseline and 3, 6, and 12 months following the active intervention period. DiscussionThe results from this study, called the SISTER (Sisters Inspiring Sisters to Engage in Relevant Diabetes Self-Care) Diabetes Study, are vital to the adoption and uptake of rigorously-tested MNT interventions that address motivation among AA women with T2D as a way to reduce their risk and/or progression of diabetes-related complications.

Time-in-range: a promising glycemic control metric for bariatric surgery.

As a complication of obesity, type 2 diabetes (T2D) is a chronic disease that is difficult to manage. However, bariatric surgery makes it possible to alleviate T2D. While the existing generic index glycosylated hemoglobin (HbA1c) is a powerful tool for examining overall blood glucose levels, it still has some limitations as a daily measure of blood glucose levels and as a judge of the effectiveness of bariatric surgery. Using the time-in-range (TIR) measurement and its derivatives is a better way to evaluate short-term blood glucose fluctuations and can be used as a supplement to HbA1c. In this article, we discuss the utility and limitations of HbA1c and other indicators used during surgery. In addition, we mentioned TIR as a novel metric that can act as an accurate predictor of the risk of T2D complications and an index of preoperative risk assessment in bariatric surgery. In contrast to previous indicators, TIR has the advantage that it cannot be affected by caloric restriction to better reflect the patient's glucose level and the level of pancreatic islet function. On this basis, TIR is a promising indicator for both the diagnosis of diabetes and the preoperative and postoperative prediction and evaluation.

Prediction of clinical events by liver stiffness and chronic kidney disease by NAFLD in patients with type-2 diabetes

Background & AimsNon-alcoholic fatty liver disease (NAFLD) is associated with poorer glycemic control and a higher risk of type-2 diabetes (T2D) complications, extrahepatic and cardiovascular disease (CVD). Our study aim was to evaluate the association between NAFLD, T2D complications, and the development of overall clinical events (OCE) (CV, liver-related, and mortality) in patients with T2D. MethodsProspective single-center study comprising T2D subjects with no history of CVD and non-T2D matched controls. Patients were selected from the Outpatient Diabetes Clinic of Vall d’Hebron Hospital and related primary care centers. Results186 diabetics and 57 controls were included. Amongst T2D, 124/186 subjects had NAFLD (66.6%). T2D-NAFLD subjects showed a heavier metabolic burden and higher median liver stiffness (5.6kPa [4.5–7.3] vs 4.8 [4.2–5.8]; p=0.004) compared to non-NAFLD diabetics. During a median follow-up of 5.6 years, 33 (17.7%) T2D patients developed OCE vs 4 (7.0%) controls (p=0.049). No differences were found for OCE between NAFLD and non-NAFLD diabetics (16.9% vs 19.4%; p=0.68). CV was the most reported outcome and only one liver event occurred. NAFLD diabetics showed more often chronic kidney disease (CKD), whereas T2D complications and subclinical CVD rates were similar. A higher liver stiffness, older age, and male gender were independently associated with OCE amongst the entire T2D population and NAFLD diabetics. ConclusionsNAFLD and liver stiffness were associated with CKD and clinical outcomes in diabetics, respectively. A hepatic evaluation is recommended to identify high-risk T2D patients that would benefit from early referral to specialized care.

Ambient air pollution associated with incidence and dynamic progression of type 2 diabetes: a trajectory analysis of a population-based cohort

BackgroundThough the association between air pollution and incident type 2 diabetes (T2D) has been well documented, evidence on the association with development of subsequent diabetes complications and post-diabetes mortality is scarce. We investigate whether air pollution is associated with different progressions and outcomes of T2D.MethodsBased on the UK Biobank, 398,993 participants free of diabetes and diabetes-related events at recruitment were included in this analysis. Exposures to particulate matter with a diameter ≤ 10 μm (PM10), PM2.5, nitrogen oxides (NOx), and NO2 for each transition stage were estimated at each participant’s residential addresses using data from the UK’s Department for Environment, Food and Rural Affairs. The outcomes were incident T2D, diabetes complications (diabetic kidney disease, diabetic eye disease, diabetic neuropathy disease, peripheral vascular disease, cardiovascular events, and metabolic events), all-cause mortality, and cause-specific mortality. Multi-state model was used to analyze the impact of air pollution on different progressions of T2D. Cumulative transition probabilities of different stages of T2D under different air pollution levels were estimated.ResultsDuring the 12-year follow-up, 13,393 incident T2D patients were identified, of whom, 3791 developed diabetes complications and 1335 died. We observed that air pollution was associated with different progression stages of T2D with different magnitudes. In a multivariate model, the hazard ratios [95% confidence interval (CI)] per interquartile range elevation in PM2.5 were 1.63 (1.59, 1.67) and 1.08 (1.03, 1.13) for transitions from healthy to T2D and from T2D to complications, and 1.50 (1.47, 1.53), 1.49 (1.36, 1.64), and 1.54 (1.35, 1.76) for mortality risk from baseline, T2D, and diabetes complications, respectively. Generally, we observed stronger estimates of four air pollutants on transition from baseline to incident T2D than those on other transitions. Moreover, we found significant associations between four air pollutants and mortality risk due to cancer and cardiovascular diseases from T2D or diabetes complications. The cumulative transition probability was generally higher among those with higher levels of air pollution exposure.ConclusionsThis study indicates that ambient air pollution exposure may contribute to increased risk of incidence and progressions of T2D, but to diverse extents for different progressions.

Continuous Glucose Monitor, Insulin Pump, and Automated Insulin Delivery Therapies for Type 1 Diabetes: An Update on Potential for Cardiovascular Benefits.

Purpose of ReviewThe incidence of type 1 diabetes (T1D) is rising in all age groups. T1D is associated with chronic microvascular and macrovascular complications but improving glycemic trends can delay the onset and slow the progression of these complications. Utilization of technological devices for diabetes management, such as continuous glucose monitors (CGM) and insulin pumps, is increasing, and these devices are associated with improvements in glycemic trends. Thus, device use may be associated with long-term prevention of T1D complications, yet few studies have investigated the direct impacts of devices on chronic complications in T1D. This review will describe common diabetes devices and combination systems, as well as review relationships between device use and cardiovascular outcomes in T1D.Recent FindingsFindings from existing cohort and national registry studies suggest that pump use may aid in improving cardiovascular risk factors such as hypertension and dyslipidemia. Furthermore, pump users have been shown to have lower arterial stiffness and better measures of myocardial function. In registry and case–control longitudinal data, pump use has been associated with fewer cardiovascular events and reduction of cardiovascular disease (CVD) and all-cause mortality.SummaryCVD is the leading cause of morbidity and mortality in T1D. Consistent use of diabetes devices may protect against the development and progression of macrovascular complications such as CVD through improvement in glycemic trends. Existing literature is limited, but findings suggest that pump use may reduce acute cardiovascular risk factors as well as chronic cardiovascular complications and overall mortality in T1D.

Exploration of the role of bound polyphenols on tea residues dietary fiber improving diabetic hepatorenal injury and metabolic disorders

Consumption of tea residues dietary fiber (TRDF) contributed to the relief of hyperglycemia symptoms in type 2 diabetes (T2D). Given the properties of TRDF abundant in bound polyphenols, the research intended to evaluate the effect of the presence or absence of bound polyphenols in TRDF on the improvement of diabetic complications (liver and kidney injury, metabolic disorders) in T2D rats induced by high-fat diet and streptozocin injection. Our results revealed that the presence of bound polyphenols in TRDF was remarkably beneficial for the amelioration of liver and kidney damage caused by T2D, which was supported by significant differences in activities of serum glutamic oxaloacetic transaminase (AST) and glutamic-pyruvic transaminase (ALT), contents of inflammatory factors in liver and kidney, the levels of kidney oxidative stress, as well as histopathological status between TRDF and bound polyphenols removed-TRDF (TRDF-DF) groups. In addition, metabolomic analysis revealed that TRDF interventions could increase the levels of metabolites such as S-Adenosylmethionine, L-Homophenylalanine and Riboflavin, as well as differ in the regulation of the metabolic pathways including arachidonic acid metabolism and cysteine and methionine metabolism as compared to TRDF-DF without bound polyphenols. These results suggested that bound polyphenols ensured the health-promoting effects for T2D complications of TRDF.

Validation of the clinical consensus recommendations on the management of fracture risk in postmenopausal women with type 2 diabetes

Background and aimsBone fragility is recognized as a complication of type 2 diabetes (T2D). However, the fracture risk in T2D is underestimated using the classical assessment tools. An expert panel suggested the diagnostic approaches for the detection of T2D patients worthy of bone-active treatment. The aim of the study was to apply these algorithms to a cohort of T2D women to validate them in clinical practice. Methods and resultsThe presence of T2D-specific fracture risk factors (T2D ≥ 10 years, ≥1 T2D complications, insulin or thiazolidinedione use, poor glycaemic control) was assessed at baseline in 107 postmenopausal T2D women. In all patients at baseline and in 34 patients after a median follow-up of 60.2 months we retrospectively evaluated bone mineral density and clinical and morphometric vertebral fractures. No patient was treated with bone-active drug. Following the protocols, 34 (31.8%) and 73 (68.2%) patients would have been pharmacologically and conservatively treated, respectively. Among 49 patients without both clinical fractures and major T2D-related risk factors, who would have been, therefore, conservatively followed-up without vertebral fracture assessment, only one showed a prevalent vertebral fracture (sensitivity 90%, negative predictive value 98%). The two patients who experienced an incident fracture would have been pharmacologically treated at baseline. ConclusionsThe clinical consensus recommendations showed a very good sensitivity in identifying T2D postmenopausal women at high fracture risk. Among those with treatment indication as many as 13% of patients experienced an incident fracture, and, conversely, among those without treatment indication no incident fractures were observed.

Socio-economic gradients in diagnosed and undiagnosed Type 2 diabetes and its related health complications

Background and aimsDiagnosed and undiagnosed Type 2 Diabetes (T2D) remains a challenge in high-income countries. In addition, the presence of T2D can cause further disease burden because of its high susceptibility to complications. Nevertheless, there is limited evidence of socio-economic gradients in undiagnosed T2D and its complications in a large population cohort. We investigated this using the Dutch Lifelines Cohort Study (Lifelines). Methods and resultsWithin Lifelines, baseline data of 102 163 adults aged 30 and above were collected from 2007 to 2013. The associations of Socio-Economic Status (SES), indicated by monthly household income, with the prevalence of T2D status and the number of T2D complications were assessed using multinomial Poisson and linear regressions with adjustments for age and sex. The prevalence of diagnosed and undiagnosed T2D was, respectively, 3.0% and 3.0% in the low SES group compared to 1.1% and 1.8% in the high SES group. Individuals with lower SES were at higher risk of having undiagnosed T2D (relative risk ratio (rrr) [95% CI]: 1.63 [1.47–1.81] for low SES and 1.16 [1.05–1.29] for middle SES) and diagnosed T2D, compared with those with high SES. Lower SES was positively associated with the number of T2D complications (low SES vs. high SES (ref); B [95% CI]: 0.15 [0.13–0.16]). ConclusionComplementing the known socio-economic gradients in diagnosed T2D, we document socio-economic gradients in undiagnosed T2D and T2D complications in a single, large general representative population. Furthermore, individuals with low SES with diagnosed or undiagnosed T2D were more susceptible to T2D complications.

Cystatin C and Chronic Complications of Diabetes Mellitus in a Subsaharian Population

Background: Type 2 diabetes (T2D) is a chronic and progressive condition whose early management is crucial in preventing the occurrence of its chronic degenerative complications. Cystatin C (CysC) is a biomarker that may have a beneficial interest in the early detection of microvascular and macrovascular complications of T2D. Methods: We carried out a cross-sectional analytic study at the National Obesity Center of the Yaounde Central Hospital. We recruited 135 patients with T2D and performed a neurologic physical exam using the Toronto clinical score, a fundoscopy, ECG, ABI, and the following paraclinicals: dosage of serum levels of Cystatin C, lipid profile (with determination of Atherogenic indexes), Creatinine (with calculation of glomerular filtration rate using CKD-EPI formula) and hs-CRP. Results: Prevalences of diabetic retinopathy, nephropathy, neuropathy and PAD were 3.0%, 8.9%, 38.5%, 28.1% respectively. Electrocardiographic signs of myocardial ischemia were present in 5.9 % of the participants. We found 0.3[0.5-0.3] mg/l as median levels of the HDL-cholesterol and 0.9[1.2-0.7] mg/l for LDL-cholesterol. The median value of GFR was 105.7[119,0-85.7] ml/min/1.73m². The median serum CysC level was 0.8[0.9-0.6]mg/l and varied with age (p=0.01), A1C (p=0.016) and high blood pressure (HBP) (p=0.006). There was a relationship between serum CysC and diabetic nephropathy (p=0.01) and neuropathy (p=0.025). There was no significant relationship with diabetic retinopathy (p=0.225), PAD (p=0.169) and ECG signs of myocardial ischemia (p=0.669). Conclusion: Chronic microvascular and macrovascular complications of type 2 diabetes are common and in our study are predominantly represented by diabetic neuropathy and PAD. Serum CysC can be useful in the diagnosis of chronic complications of T2D.

Biochemical and clinical markers of endothelial dysfunction do not outweigh traditional risk factors for the presence of diabetic retinopathy in patients with type 1 diabetes

BackgroundThis study aimed to evaluate whether soluble vascular cytoadhesive molecule-1 (sVCAM-1), intracellular cytoadhesive molecule-1 (sICAM-1), and endothelial function as assessed by EndoPat outweighed traditional risk factors for the presence of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D).MethodsPatients aged ≥ 12 years completed a clinical–epidemiological questionnaire. Fasting venous blood samples were obtained (lipid profile, glycemic control, and C-reactive protein levels). Vascular reactivity was assessed via peripheral arterial tonometry performed by supplying the reactive hyperemia index (RHI) through the EndoPAT device. sVCAM-1 and sICAM-1 levels were measured using multiplex assays.ResultsData were obtained from 187 patients (51.3% female), aged 32 ± 13 years with a disease duration of 14 (6–15) years and mean hemoglobin A1c (HbA1c) of 9.1% ± 2.1%. After adjustments were made, age, HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function were found to be associated with DR. No association was noted with sVCAM-1 and sICAM-1 levels and RHI.ConclusionsIn our sample, sVCAM-1, sICAM and EndoPAT did not outweigh the traditional DR risk factors, such as age, high HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function and are significantly associated with DR. Further prospective studies should evaluate if markers of endothelial dysfunction could predict diabetes-related micro and macrovascular complications in T1D.

Evaluation of the therapeutic efficacy of dressings with ZnO nanoparticles in the treatment of diabetic foot ulcers

Type 2 diabetes (T2D) in developed countries have a prevalence of 11% with diabetic foot infections as the most common cause of hospitalization and amputation. To achieve healing of the diabetic foot ulcer wounds, appropriate dressings are essential and their effectiveness can be enhanced with nanoparticles, nevertheless ideal combinations of dressing composition and nanodrugs require further testing in humans. We have developed a calcium alginate dressings with ZnO nanoparticles (CAZnODs) for the treatment of diabetic foot ulcers in human patients. To test the efficacy of CAZnODs we designed a randomized controlled clinical experiment on 26 T2D patients with foot ulcers. The patients were randomized into two groups: G1 treatment with calcium alginate with NPs (G1; n = 16), and group 2 received the treatment without NPs (G2, n = 10). The bandage change was performed every 48 h The duration of the protocol was established at 10 weeks. Here, we report healing was achieved in patients, with 75% wound closure in G1 under treatment with NPs of calcium alginate versus 71% in G2 (calcium alginate without NPs) (p = 0.011). The average healing time was 48 days in G1 and 72 days in G2. Our data shows that CAZnODs were well tolerated and did not interfere with the wound healing process. The final wound area and time of healing support the hypothesis that the use of calcium alginate dressings with nanoparticles may induce better tissue regeneration while avoiding T2D complications such as secondary infections.