Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications

Aims  The Michigan Neuropathy Screening Instrument (MNSI) is used to assess distal symmetrical peripheral neuropathy in diabetes. It includes two separate assessments: a 15‐item self‐administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes. The purpose of this study was to evaluate the performance of the MNSI in detecting distal symmetrical peripheral neuropathy in patients with Type 1 diabetes and to develop new scoring algorithms. Methods  The MNSI was performed by trained personnel at each of the 28 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications clinical sites. Neurologic examinations and nerve conduction studies were performed during the same year. Confirmed clinical neuropathy was defined by symptoms and signs of distal symmetrical peripheral neuropathy based on the examination of a neurologist and abnormal nerve conduction findings in ≥ 2 anatomically distinct nerves among the sural, peroneal and median nerves. Results  We studied 1184 subjects with Type 1 diabetes. Mean age was 47 years and duration of diabetes was 26 years. Thirty per cent of participants had confirmed clinical neuropathy, 18% had ≥ 4 and 5% had ≥ 7 abnormal responses on the MNSI questionnaire, and 33% had abnormal scores (≥ 2.5) on the MNSI examination. New scoring algorithms were developed and cut points defined to improve the performance of the MNSI questionnaire, examination and the combination of the two. Conclusions  Altering the cut point to define an abnormal test from ≥ 7 abnormal to ≥ 4 abnormal items improves the performance of the MNSI questionnaire. The MNSI is a simple, non‐invasive and valid measure of distal symmetrical peripheral neuropathy in Type 1 diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92152/1/j.1464-5491.2012.03644.x.pd

Children with type 1 diabetes: where are we at?

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Jennifer J Coupe

'Join us on our journey': Exploring the experiences of children and young people with type 1 diabetes and their parents

This paper focuses on children and young people with type 1 diabetes and on their parents, and their experiences of diabetes care provision. Nine acute hospitals in the Yorkshire and the Humber region, UK, were recruited to participate in a qualitative research study. Children and young people with type 1 diabetes, aged 6–25, and their parents (approximately 250 participants), took part in talking groups to find out about their experiences of diabetes care provision. Findings show that there are key areas for improvement in the future diabetes care provision for children and young people, including communication and support, schools, structured education and transition. These have important implications for practice and service redesign. This study is thought to be the first of its kind to consult with children, young people and parents to find out about their experiences of type 1 diabetes care provision. The research findings add to the current evidence base by highlighting the disparities in care, the urgent need for change in the way services are delivered and the involvement of service users in this process

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus

BackgroundSitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.MethodsWe obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.ResultsWe classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group.ConclusionIn Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders

HbA_1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes

Aim: Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups. Methods: People with Type 1 diabetes were identified for inclusion from the Scottish Care Information – Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47‐month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables. Results: Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow‐up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25–1.45) over 730 days of follow‐up (P < 0.001). Conclusion: Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes

Prevalence of Chronic Complications in Korean Patients with Type 2 Diabetes Mellitus Based on the Korean National Diabetes Program

BackgroundThe Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years.MethodsThis study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics.ResultsAmong the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects.ConclusionThe prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females

Biomarkers of tubulointerstitial damage and function in type 1 diabetes

Objective To evaluate biomarkers of renal tubulointerstitial damage and function in type 1 diabetes with and without diabetic kidney disease. Research design and methods Cross-sectional case-control study of Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants. Cases (N=43) had incident persistent estimated glomerular filtration rate (eGFR) \u3c60 mL/min/1.73 m2 with urinary albumin excretion \u3e300 mg/24 hour. Controls (N=43) had persistent eGFR \u3e90 mL/min/1.73 m2 and urinary albumin excretion \u3c30 mg/24 hour. Urinary and plasma biomarkers reflecting tubular injury, inflammation, fibrosis, secretion, and synthetic function were measured from stored specimens collected at the first study visit with reduced eGFR (for case participants) or the corresponding study year (for control participants). Results Mean (SD) age was 51 (9) and 50 (8) years for case and control participants, and mean (SD) duration of diabetes was 30 (6) and 30 (5) years, respectively. Mean (SD) eGFR was 39 (14) and 103 (9) mL/min/1.73 m2 for case and control participants, and mean (SD) albumin excretion rate was 1978 (2914) and 10 (7) mg/day, respectively. Comparing cases with controls, significant differences were observed in each measured biomarker, including urine epidermal growth factor (mean 5.3 vs 21.2 μg/g creatinine for case vs control participants, respectively), urine monocyte chemoattractant protein-1 (596 vs 123 ng/g creatinine), urine galectin-3 (168 vs 52 μg/g creatinine), plasma soluble tubular necrosis factor receptor-1 (3695 vs 1022 pg/mL), plasma galectin-3 (21.3 vs 11.0 ng/mL), urinary clearances of hippurate (70 vs 167 mL/min) and cinnamoylglycine (77 vs 317 mL/min), and plasma arginine-citrulline ratio (5.6 vs 7.7 μg/μg), each P\u3c0.001. Conclusions Marked abnormalities in biomarkers of kidney tubular injury, inflammation, fibrosis, secretion, and synthetic function accompany reduced eGFR and albuminuria in type 1 diabetes. Trial registration number NCT00360893, NCT00360815

Complication characteristics between young-onset type 2 versus type 1 diabetes in a UK population.

BACKGROUND: In the UK, the care of young people with diabetes has focused predominantly on type 1 diabetes (T1D). However, young-onset T2D has become increasingly prevalent. At present, it is unclear which type of diabetes represents the more adverse phenotype to develop complications. This study aims to determine the complication burden and its predictive factors in young-onset T2D compared with T1D. METHODS: A cross-sectional study using a hospital diabetes register to identify patients with young-onset T2D and T1D. Young-onset T2D was defined as age of diagnosis below 40 years. The T1D cohort with a similar age of diagnosis was used as a comparator. Data from the last clinic visit was used for analysis. Clinical characteristics and diabetes complications were evaluated at diabetes durations 20 years. Predictive factors for diabetes complications (age, sex, glycated hemoglobin, creatinine, diabetes duration, hypertension, dyslipidemia, and body mass index >25) were determined by logistic regression analysis. RESULTS: Data were collected on 1287 patients, of which 760 and 527 had T1D and T2D, respectively. In all diabetes durations, the T2D cohort had an older age of onset (p<0.0005) with a higher prevalence of obesity, hypertension, and dyslipidemia (all p<0.0005) while glycemic control was similar in both groups. Cardiovascular disease (p<0.005) and neuropathy (p<0.05) were more prevalent in the young-onset T2D cohort in all diabetes durations. There was no difference in retinopathy. Cardiovascular disease was predominantly due to ischemic heart disease. Stroke and peripheral vascular disease became significantly higher in T2D after 20 years duration. After controlling for traditional risk factors, young-onset T2D was an independent predictor for cardiovascular disease (p<0.005) and neuropathy (p<0.05) but not for retinopathy. CONCLUSIONS: Young-onset T2D is a more aggressive phenotype than T1D to develop diabetes complications, particularly for ischemic heart disease and neuropathy

One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial

P>Aim: The aim of this study was to compare the efficacy and safety of once-daily human glucagon-like peptide-1 analogue liraglutide with dipeptidyl peptidase-4 inhibitor sitagliptin, each added to metformin, over 52 weeks in individuals with type 2 diabetes. Methods: In an open-label, parallel-group trial, metformin-treated participants were randomised to liraglutide 1.2 mg/day (n = 225), liraglutide 1.8 mg/day (n = 221) or sitagliptin 100 mg/day (n = 219) for 26 weeks (main phase). Participants continued the same treatment in a 26-week extension. Results: Liraglutide (1.2 or 1.8 mg) was superior to sitagliptin for reducing HbA(1c) from baseline (8.4-8.5%) to 52 weeks: -1.29% and -1.51% vs. -0.88% respectively. Estimated mean treatment differences between liraglutide and sitagliptin were as follows: -0.40% (95% confidence interval -0.59 to -0.22) for 1.2 mg and -0.63% (-0.81 to -0.44) for 1.8 mg (both p < 0.0001). Weight loss was greater with liraglutide 1.2 mg (-2.78 kg) and 1.8 mg (-3.68 kg) than sitagliptin (-1.16 kg) (both p < 0.0001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly more with liraglutide 1.8 mg than with sitagliptin (p = 0.03). Proportions of participants reporting adverse events were generally comparable; minor hypoglycaemia was 8.1%, 8.3% and 6.4% for liraglutide 1.2 mg, 1.8 mg and sitagliptin respectively. Gastrointestinal side effects, mainly nausea, initially occurred more frequently with liraglutide, but declined after several weeks. Conclusion: Liraglutide provides greater sustained glycaemic control and body weight reduction over 52 weeks. Treatment satisfaction was significantly greater with 1.8 mg liraglutide, similar to 26-week results. The safety profiles of liraglutide and sitagliptin are consistent with previous reports

Levels of Oxidized LDL and Advanced Glycation End Products–Modified LDL in Circulating Immune Complexes Are Strongly Associated With Increased Levels of Carotid Intima-Media Thickness and Its Progression in Type 1 Diabetes

OBJECTIVE High cholesterol levels in circulating immune complexes (IC), surrogate markers of modified LDL, are associated with increased carotid intima-media thickness (IMT) and cardiovascular events in type 1 diabetes. Different modifications of LDL are involved in IC formation, but which of these are predictive of vascular events is not known. Therefore, we measured oxidized LDL (oxLDL), advanced glycation end products–modified LDL (AGE-LDL), and malondialdehyde-modified LDL (MDA-LDL) in IC and determined their relationship with increased carotid IMT and compared the strength of the association with that observed with conventional risk factors. RESEARCH DESIGN AND METHODS Levels of oxLDL, AGE-LDL, and MDA-LDL were measured in circulating IC isolated from sera of 479 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort, collected at baseline. Internal and common carotid IMT were measured 8 and 14 years later by DCCT/EDIC. RESULTS OxLDL, AGE-LDL, and MDA-LDL levels in circulating IC were significantly correlated with diabetes duration, BMI, and lipid and blood pressure, but not with age. Multivariate logistic regression models indicated that individuals in the highest versus lowest quartile of oxLDL and AGE-LDL in IC had a 6.11-fold [confidence interval (CI) 2.51–14.8] and a 6.4-fold (CI 2.53–16.2) increase in the odds of having high carotid IMT, respectively, after adjusting for conventional risk factors. Parallel analyses resulted in odds ratios of 2.62 (CI 1.24, 5.55) for LDL-C, 1.45 (CI 0.69, 3.03) for diastolic blood pressure, and 2.33 (CI 1.09, 4.99) for A1C. CONCLUSIONS OxLDL and AGE-LDL in circulating IC were significantly associated with progression and increased levels of carotid IMT in type 1 diabetes