A 6-year nationwide cohort study of glycaemic control in young people with type 1 diabetes. Risk markers for the development of retinopathy, nephropathy and neuropathy. Danish Study Group of Diabetes in Childhood

The study aimed to identify risk markers (present at the start of the study in 1989) for the occurrence and progression of microvascular complications 6 years later (in 1995) in a Danish nationwide cohort of children and adolescents with Type 1 diabetes (average age at entry 13.7 years). Probabilities for the development of elevated albumin excretion rate (AER), retinopathy, and increased vibration perception threshold (VPT) could then be estimated from a stepwise logistic regression model. A total of 339 patients (47% of the original cohort) were studied. Sex, age, diabetes duration, insulin regimen and dose, height, weight, HbA_1c, blood pressure, and AER were recorded. In addition, information on retinopathy, neuropathy (VPT), and anti-hypertensive treatment was obtained at the end of the study. HbA_1c (normal range 4.3–5.8, mean 5.3%) and AER (upper normal limit <20 μg min⁻¹) in two, timed overnight urine collections were analysed centrally. Eye examination was performed by two-field fundus photography. Determination of VPT was assessed by biothesiometry. Increased AER (≥20 μg min⁻¹) was found in 12.8% of the patients in 1995, and risk markers for this were increased AER and high HbA_1c, in 1989 (both p<0.001). Retinopathy was present in 57.8% of patients in 1995, for which the risk markers were long duration of diabetes (p<0.0001), age (p<0.01), and high HbA_1c (p<0.0001) in 1989. Elevated VPT (>6.5 V) was found in 62.5% of patients in 1995, for which the risk markers were male sex (p<0.05), age (p<0.0001), and increased AER (p<0.05) in 1989. This study confirms that hyperglycaemia plays a major role for the development of microvascular complications in kidneys and eyes, and emphasises the need for optimal glycaemic control in children and adolescents with Type 1 diabetes.     

Lp(a) and Apo-lipoproteins as predictors for micro- and macrovascular complications of diabetes: A case-cohort study

AimsTo investigate the associations between Lp(a), Apo A1, Apo B, and Apo B/Apo A1 ratio with micro- and macrovascular complications of diabetes.Methods and resultsIn this case-cohort study, 1057 patients with type 2 diabetes (T2DM) were followed in the diabetes clinic of Vali-Asr Hospital from 2014 to 2019. The association between serum Lp (a) and apolipoproteins with cardiovascular disease (CVD), neuropathy, and nephropathy were assessed by using binary regression analysis. The ROC curve analysis was used to evaluate the predictive properties of proteins. Youden index was used to calculate cutoff values. Among patients with T2DM, 242, 231, and 91 patients developed CVD, neuropathy, and nephropathy, respectively. The serum Lp (a) level was positively correlated with the development of all three. (P-values = 0.022, 0.042, and 0.038, respectively). The Apo A1 level was negatively correlated with nephropathy. Among the biomarkers, Lp(a) had the highest AUC for prediction of CVD, neuropathy, and nephropathy. Calculated cutoff values of Lp(a), and Apo A1 levels were higher than the standard cutoff values.ConclusionSerum level of Lp(a) is a predictor for CVD, neuropathy, and nephropathy. Based on the calculated cutoff values in patients with T2DM, we should consider diabetic complications at higher levels of Lp(a).     

Determinants of glycemic control: Phase 2 analysis from nationwide diabetes report of National Program for Prevention and Control of Diabetes (NPPCD-2018)

BackgroundDiabetes is one of the leading causes of morbidity and mortality worldwide, especially among middle and low income nations. Many diabetic complications and comorbidities are attributable to poor glycemic control. The aim of this study was to update and extend the national diabetes reports on the status of comorbidities, diabetes care and complications in Iran. Moreover, we investigated the risk factors of poor glycemic control in the Iranian population.MethodsNational database of 99,651 patients with diabetes who attended university-affiliated clinics between April 1, 2017 and February 30, 2018 was used to carry out a cross-sectional study. Stepwise backward selection logistic regression model was used to examine the associated factors of glycemic control.ResultsIn this study 73.0% and 56.5% of the enrolled population with diabetes, had hypertension and hyperlipidemia, respectively. The prevalence of patients who received education for nutrition therapy or diabetes self-management was 16.3% and 23.3% respectively. Poor glycemic control was associated with male gender (OR = 1.06, p = 0.001), obesity (OR = 1.03, p = 0.05), duration of diabetes (OR = 1.018, p < 0.001), smoking (OR = 1.08, p = 0.041), hypertension (OR = 1.53, p < 0.001), hyperlipidemia (OR = 1.15, p < 0.001), insulin therapy (OR = 1.26, p < 0.001) and combination of insulin and oral anti-diabetic agents compared to oral anti-diabetic agents alone (OR = 2.36, p < 0.001).ConclusionWe demonstrated that the prevalence of diabetes comorbidities is high in Iranian population and that a great proportion of Iranian patients with diabetes had not reached the goal of glycemic control. Our findings provide a starting point from which to investigate the obstacles that prevent patients with diabetes from reaching metabolic targets.     

Glycated albumin and the risk of chronic kidney disease in subjects with Type 2 Diabetes: A study in North Indian Population

Aim

Glycated albumin (GA) suggested being alternative glycemic marker than haemoglobin A1C (HbA1c) in patients with chronic kidney diseases (CKD). We investigated the association between GA and the progression of diabetic nephropathy (DN) in T2DM subjects.

Cost-effectiveness of primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes: results from the Collaborative Atorvastatin Diabetes Study (CARDS)

Aims/hypothesis We estimated the cost-effectiveness of atorvastatin treatment in the primary prevention of cardiovascular disease in patients with type 2 diabetes using data from the Collaborative Atorvastatin Diabetes Study (CARDS). Subjects and methods A total of 2,838 patients, who were aged 40 to 75 years and had type 2 diabetes without a documented history of cardiovascular disease and without elevated LDL-cholesterol, were recruited from 32 centres in the UK and Ireland and randomly allocated to atorvastatin 10 mg daily (n = 1,428) or placebo (n = 1,410). These subjects were followed-up for a median period of 3.9 years. Direct treatment costs and effectiveness were analysed to provide estimates of cost per endpoint-free year over the trial period for alternative definitions of endpoint, and of cost per life-year gained and cost per quality-adjusted life-year (QALY) gained over a patient’s lifetime. Results Over the trial period, the incremental cost-effectiveness ratio (ICER) was estimated to be ￡7,608 per year free of any CARDS primary endpoint; the ICER was calculated to be ￡4,896 per year free of any cardiovascular endpoint and ￡4,120 per year free of any study endpoint. Over lifetime, the incremental cost per life-year gained was ￡5,107 and the cost per QALY was ￡6,471 (costs and benefits both discounted at 3.5%). Conclusions/interpretation Primary prevention of cardiovascular disease with atorvastatin is a cost-effective intervention in patients with type 2 diabetes, with the ICER for this intervention falling within the current acceptance threshold (￡20,000 per QALY) specified by the National Institute for Health and Clinical Excellence (NICE). Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.     

UK Prospective Diabetes Study. IV. Characteristics of Newly presenting Type 2 Diabetic Patients: Male Preponderance and Obesity at Different Ages

The characteristics of newly presenting Type 2 diabetes mellitus have been examined in 1857 newly diagnosed diabetic patients aged 25–65 years inclusive. The males were less obese than the females (121% vs 141% IBW, respectively), but a male-dominated sex ratio of 1.54 was found. Taking into account the prevalence of obesity in the general population, males had a 2.5-fold relative risk of presenting with diabetes, although with increasing obesity the male preponderance was lost. Presentation increased with age up to the age of 55 years. Patients presenting at all ages had similar glycaemia and were similarly obese. Those presenting at a younger age were usually particularly obese in relation to the general population. Obese patients were less physically active than normal weight patients. Type 2 diabetes had a seasonal variation of presentation with a peak in January to April.     

Subclinical diabetic neuropathy: similarities between electrophysiological results of patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus

Summary Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients share many clinical and biochemical characteristics. However, sural nerve biopsies from patients with advanced and chronic neuropathy show ultrastructural differences between these two groups. We investigated whether at a subclinical stage of the illness, when Type 1 and Type 2 diabetic patients are clinically uniform and the histopathological nerve alterations are not advanced, comparison between the two diabetes groups might show differences in nerve fibre involvement related to the different pathogeneses of the neuropathies. A total of 88 diabetic patients (52 Type 1 and 36 Type 2), with a subclinical form of polyneuropathy were selected. The clinical neurophysiological examination consisted of motor and sensory nerve conduction studies, Hoffmann (H)-reflex, single fibre electromyography and static as well as dynamic pupillometry. With regard to clinical neurophysiological abnormalities, the severity of the polyneuropathy appeared to be equal in both groups. Despite the absence of clinical symptoms the neurophysiological abnormalities were pronounced and it was impossible to differentiate Type 1 diabetic patients from Type 2 diabetic patients on a clinical neurophysiology basis when correcting for differences in age, height, and duration of illness. In the Type 1 diabetic group as well as in the Type 2 diabetic group the autonomic nerve fibres and nerves in the legs were more frequently affected than the thick myelinated nerves in the arms. These findings do not support the assumption that there is a difference in the manifestation of polyneuropathy between Type 1 and Type 2 diabetic patients.     

Cardiovascular risk management in type 2 diabetes mellitus: A joint position paper of the Italian Cardiology (SIC) and Italian Diabetes (SID) Societies

AimThis review represents a joint effort of the Italian Societies of Cardiology (SIC) and Diabetes (SID) to define the state of the art in a field of great clinical and scientific interest which is experiencing a moment of major cultural advancements, the cardiovascular risk management in type 2 diabetes mellitus.Data synthesisConsists of six chapters that examine various aspects of pathophysiology, diagnosis and therapy which in recent months have seen numerous scientific innovations and several clinical studies that require extensive sharing.ConclusionsThe continuous evolution of our knowledge in this field confirms the great cultural vitality of these two cultural spheres, which requires, under the leadership of the scientific Societies, an ever greater and effective collaboration.     

Complications of type 2 diabetes mellitus in Ramallah and al-Bireh: The Palestinian Diabetes Complications and Control Study (PDCCS)

Background

Type 2 diabetes mellitus (T2DM) is a growing pandemic that will lead, if not managed and controlled, to frequent complications, poor quality of life, and high rates of disability and death. Little is known about T2DM complications in Palestine. The aim of this study is to estimate the prevalence of T2DM complications in Ramallah and al-Bireh governorate of Palestine.

Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS)

Aims/hypothesis  Controversy surrounds whether the ratio of apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) is the best lipoprotein discriminator of CHD risk in non-diabetic populations, but the issue has never been investigated in type 2 diabetes. Methods  In 2,627 participants without known vascular disease in the Collaborative Atorvastatin Diabetes Study, ApoB, ApoA-I, LDL-cholesterol (LDLC) and HDL-cholesterol (HDLC) were assayed at baseline. Results  There were 108 CHD and 59 stroke endpoints over 3.9 years. The ApoB:A-I ratio at baseline was the lipoprotein variable most closely predicting CHD risk both by comparison of the hazard ratio for a 1 SD change or tertiles of frequency distribution. The areas under the receiver–operator curve for the ApoB:ApoA-I and the LDLC to HDL-HDLC ratios, although not significantly different from each other, were greater (p = 0.0005 and p = 0.0125 respectively) than that of non-HDLC:HDLC. The 27% decrease in the ApoB:ApoA-I ratio on atorvastatin predicted a 32% (95% CI 5.4–51.2%) risk reduction in CHD, close to the 36% decrease observed. Neither the ApoB:ApoA-I nor any other lipoprotein concentration or ratio predicted the stroke outcome. Conclusions/interpretation  Overall, the ApoB:ApoA-I ratio improved on the non-HDLC:HDLC ratio in predicting CHD, but, depending on the assessment chosen, its superiority over LDLC:HDLC may be marginal. The statin-induced decrease in stroke risk may not be lipoprotein mediated. Trial registration: ClinicalTrials.gov NCT00327418 Funding: The study was supported by unrestricted grants from Diabetes UK, the Department of Health and Pfizer to the University of Manchester and to University College, London. An erratum to this article can be found at     

Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol

Aims/hypothesis Studies suggest that in addition to blood glucose concentrations, thiazolidinediones such as rosiglitazone improve some cardiovascular (CV) risk factors and surrogate markers, that are abnormal in type 2 diabetes. However, fluid retention might lead to cardiac failure in a minority of people. The aim of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study is to evaluate the long-term impact of these effects on CV outcomes, as well as on long-term glycaemic control, in people with type 2 diabetes.Materials and methods RECORD is a 6-year, randomised, open-label study in type 2 diabetic patients with inadequate blood glucose control (HbA₁c 7.1–9.0%) on metformin or sulphonylurea alone. The study is being performed in 327 centres in Europe and Australasia. After a 4-week run-in, participants were randomised by current treatment stratum to add-on rosiglitazone, metformin or sulphonylurea, with dose titration to a target HbA₁c of 7.0%. If confirmed HbA₁c rises to 8.5%, either a third glucose-lowering drug is added (rosiglitazone-treated group) or insulin is started (non-rosiglitazone group). The same criterion for failure of triple oral drug therapy in the rosiglitazone-treated group is used for starting insulin in this group. The primary endpoint is the time to first CV hospitalisation or death, blindly adjudicated by a central endpoints committee. The study aim is to evaluate non-inferiority of the rosiglitazone group vs the non-rosiglitazone group with respect to CV outcomes. Safety, tolerability and study conduct are monitored by an independent board. All CV endpoint and safety data are held and analysed by a clinical trials organisation, and are not available to the study investigators while data collection is open.Results Over a 2-year period a total of 7,428 people were screened in 25 countries. Of these, 4,458 were randomised; 2,228 on background metformin, 2,230 on background sulphonylurea. Approximately half of the participants are male (52%) and almost all are Caucasian (99%).Conclusions/interpretation The RECORD study should provide robust data on the extent to which rosiglitazone, in combination with metformin or sulphonylurea therapy, affects CV outcomes and progression of diabetes in the long term.     

Do plasminogen activator inhibitor (PAI-1) or tissue plasminogen activator PAI-1 complexes predict complications in Type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study.

AIMS: To examine the predictive power of plasminogen activator inhibitor-1 (PAI-1) and the complexes it forms with tissue plasminogen activator (tPA-PAI-1) for the two major Type 1 diabetes (T1D) complications (coronary artery disease (CAD) and overt nephropathy) in the context of standard risk factors. METHODS: Observational prospective study of 454 participants with childhood onset (< 17 years) T1D, aged 18+ years at baseline. PAI-1 and tPA-PAI-1 were determined using ELISA methodology. Follow-up (6 years) was limited to 382 individuals for CAD and 294 individuals for overt nephropathy, after excluding baseline cases. Total, HDL and LDL-cholesterol, triglycerides, HbA1, blood pressure, body mass index (BMI), waist-hip ratio (WHR), leucocyte count, Beck depression score and fibrinogen were also examined. RESULTS: The 56 incident cases of CAD had marginally lower PAI-1 and higher tPA-PAI-1 levels compared with those free of CAD. However, marginally higher PAI-1 and significantly higher tPA-PAI-1 (P = 0.04) levels were seen in those who developed nephropathy. After controlling for age, both PAI-1 and tPA-PAI-1 showed significant negative correlations with HDL-cholesterol, and positive correlations with triglycerides, WHR, HbA1 and fibrinogen. tPA-PAI-1 was also positively correlated with total and LDL-cholesterol. In multivariate analyses, neither PAI-1 nor tPA-PAI-1 was an independent predictor of CAD or overt nephropathy. CONCLUSIONS: These results suggest little association between PAI-1 and later CAD in patients with T1D. However, tPA-PAI-1 complexes may be involved in the pathogenesis of overt nephropathy.     

Diagnostic criteria for acute‐onset type 1 diabetes mellitus (2012): Report of the Committee of Japan Diabetes Society on the Research of Fulminant and Acute‐onset Type 1 Diabetes Mellitus

Type 1 diabetes is a disease characterized by destruction of pancreatic β‐cells, which leads to absolute deficiency of insulin secretion. Depending on the manner of onset and progression, it is classified as fulminant, acute‐onset or slowly progressive type 1 diabetes. Here, we propose the diagnostic criteria for acute‐onset type 1 diabetes mellitus. Among the patients who develop ketosis or diabetic ketoacidosis within 3 months after the onset of hyperglycemic symptoms and require insulin treatment continuously after the diagnosis of diabetes, those with anti‐islet autoantibodies are diagnosed with ‘acute‐onset type 1 diabetes mellitus (autoimmune)’. In contrast, those whose endogenous insulin secretion is exhausted (fasting serum C‐peptide immunoreactivity <0.6 ng/mL) without verifiable anti‐islet autoantibodies are diagnosed simply with ‘acute‐onset type 1 diabetes mellitus’. Patients should be reevaluated after certain periods in case their statuses of anti‐islet autoantibodies and/or endogenous insulin secretory capacity are unknown.     

Bone fragility in patients with diabetes mellitus: A consensus statement from the working group of the Italian Diabetes Society (SID), Italian Society of Endocrinology (SIE), Italian Society of Gerontology and Geriatrics (SIGG), Italian Society of Orthopaedics and Traumatology (SIOT)

Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects.Considering the complexity of diabetes and osteoporosis and the range of variables that influence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A)ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.     

Changes in glycaemic control and risk of coronary artery disease in type 1 diabetes mellitus: findings from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC)

Aims/hypothesis To complete a comparative analysis of studies that have examined the relationship between glycaemia and cardiovascular disease (CVD)/coronary artery disease (CAD) and perform a prospective analysis of the effect of change in glycosylated Hb level on CAD risk in the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of childhood-onset type 1 diabetes mellitus (n = 469) over 16 years of two yearly follow-up. Methods Measured values for HbA₁ and HbA_1c from the EDC were converted to the DCCT-standard HbA_1c for change analyses and the change in HbA_1c was calculated (final HbA_1c minus baseline HbA_1c). CAD was defined as EDC-diagnosed angina, myocardial infarction, ischaemia, revascularisation or fatal CAD after medical record review. Results The comparative analysis suggested that glycaemia may have a stronger effect on CAD in patients without, than in those with, albuminuria. In EDC, the change in HbA_1c differed significantly between CAD cases (+0.62 ± 1.8%) and non-cases (−0.09 ± 1.9%) and was an independent predictor of CAD. Conclusions/interpretation Discrepant study results regarding the relationship of glycaemia with CVD/CAD may, in part, be related to the prevalence of renal disease. Measures of HbA_1c change over time show a stronger association with CAD than baseline values.     

PREDIRCAM eHealth Platform for Individualized Telemedical Assistance for Lifestyle Modification in the treatment of Obesity,Diabetes, and Cardiometabolic Risk Prevention: A Pilot Study (PREDIRCAM 1)

Background

Healthy diet and regular physical activity are powerful tools in reducing diabetes and cardiometabolic risk. Various international scientific and health organizations have advocated the use of new technologies to solve these problems. The PREDIRCAM project explores the contribution that a technological system could offer for the continuous monitoring of lifestyle habits and individualized treatment of obesity as well as cardiometabolic risk prevention.

Methods

PREDIRCAM is a technological platform for patients and professionals designed to improve the effectiveness of lifestyle behavior modifications through the intensive use of the latest information and communication technologies. The platform consists of a web-based application providing communication interface with monitoring devices of physiological variables, application for monitoring dietary intake, ad hoc electronic medical records, different communication channels, and an intelligent notification system. A 2-week feasibility study was conducted in 15 volunteers to assess the viability of the platform.

Results

The website received 244 visits (average time/session: 17 min 45 s). A total of 435 dietary intakes were recorded (average time for each intake registration, 4 min 42 s ± 2 min 30 s), 59 exercises were recorded in 20 heart rate monitor downloads, 43 topics were discussed through a forum, and 11 of the 15 volunteers expressed a favorable opinion toward the platform. Food intake recording was reported as the most laborious task. Ten of the volunteers considered long-term use of the platform to be feasible.

Conclusions

The PREDIRCAM platform is technically ready for clinical evaluation. Training is required to use the platform and, in particular, for registration of dietary food intake.